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Importance: The prevalence of iron deficiency varies widely according to how it is defined. Objective: To compare the prevalence of iron deficiency among women using 3 different definitions. Design, Setting, and Participants: The cross-sectional Hemochromatosis and Iron Overload Screening Study (HEIRS; 2000-2006) evaluated the prevalence, determinants, and outcomes of hemochromatosis and other iron-related disorders. Multiethnic, primary care-based screening (2001-2003) was performed at 5 field centers (4 in the US and 1 in Canada). Volunteer women aged 25 years and older were recruited at primary care venues associated with the field centers. Data were analyzed from June to December 2023. Main Outcomes and Measures: Measures included transferrin saturation, serum ferritin level, and self-reported age, pregnancy, and race and ethnicity. Three iron deficiency definitions were studied: (1) combined transferrin saturation less than 10% and serum ferritin less than 15 ng/mL (HEIRS), (2) serum ferritin less than 15 ng/mL (World Health Organization [WHO]), and (3) serum ferritin less than 25 ng/mL (a threshold for iron-deficient erythropoiesis [IDE]). Results: Among 62â¯685 women (mean [SD] age, 49.58 [14.27] years), 1957 women (3.12%) had iron deficiency according to the HEIRS definition, 4659 women (7.43%) had iron deficiency according to the WHO definition, and 9611 women (15.33%) had iron deficiency according to the IDE definition. Among 40â¯381 women aged 25 to 54 years, 1801 women (4.46%) had iron deficiency according to HEIRS, 4267 women (10.57%) had iron deficiency according to WHO, and 8573 women (21.23%) had iron deficiency according to IDE. Prevalence rates of iron deficiency among 2039 women aged 25 to 44 years who reported pregnancy were 5.44% (111 women) according to HEIRS, 18.05% (368 women) according to WHO, and 36.10% (736 women) according to IDE. Iron deficiency prevalence by the 3 respective definitions increased significantly in each racial and ethnic group and was significantly higher among Black and Hispanic participants than Asian and White participants. The relative iron deficiency prevalence among the 62â¯685 women increased 2.4-fold (95% CI, 2.3-2.5; P < .001) using the WHO definition and increased 4.9-fold (95% CI, 4.7-5.2; P < .001) using the IDE definition. Conclusions and Relevance: Three definitions of iron deficiency were associated with significantly different prevalence of iron deficiency in women, regardless of self-reported age, pregnancy, or race and ethnicity. Using higher serum ferritin thresholds to define iron deficiency could lead to diagnosis and treatment of more women with iron deficiency and greater reduction of related morbidity.
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Anemia Ferropriva , Ferritinas , Humanos , Feminino , Prevalência , Canadá/epidemiologia , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Anemia Ferropriva/epidemiologia , Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Ferritinas/sangue , Transferrina/análise , Transferrina/metabolismo , Gravidez , Deficiências de Ferro , IdosoRESUMO
BACKGROUND: IgG subclass levels in hemochromatosis are incompletely characterized. METHODS: We characterized IgG subclass levels of referred hemochromatosis probands with HFE p.C282Y/p.C282Y (rs1800562) and human leukocyte antigen (HLA)-A and -B typing/haplotyping and compared them with IgG subclass levels of eight published cohorts of adults unselected for hemochromatosis. RESULTS: There were 157 probands (82 men, 75 women; mean age 49±13 y). Median serum ferritin, mean body mass index (BMI), median IgG4, and median phlebotomy units to achieve iron depletion were significantly higher in men. Diabetes, cirrhosis, and HLA-A*03,-B*44, -A*03,B*07, and -A*01,B*08 prevalences and median absolute lymphocyte counts in men and women did not differ significantly. Mean IgG subclass levels [95% confidence interval] were: IgG1 5.31 g/L [3.04, 9.89]; IgG2 3.56 g/L [1.29, 5.75]; IgG3 0.61 g/L [0.17, 1.40]; and IgG4 0.26 g/L [<0.01, 1.25]. Relative IgG subclasses were 54.5%, 36.6%, 6.3%, and 2.7%, respectively. Median IgG4 was higher in men than women (0.34 g/L [0.01, 1.33] vs. 0.19 g/L [<0.01, 0.75], respectively; p = 0.0006). A correlation matrix with Bonferroni correction revealed the following positive correlations: IgG1 vs. IgG3 (p<0.01); IgG2 vs. IgG3 (p<0.05); and IgG2 vs. IgG4 (p<0.05). There was also a positive correlation of IgG4 vs. male sex (p<0.01). Mean IgG1 was lower and mean IgG2 was higher in probands than seven of eight published adult cohorts unselected for hemochromatosis diagnoses. CONCLUSIONS: Mean IgG subclass levels of hemochromatosis probands were 5.31, 3.56, 0.61, and 0.26 g/L, respectively. Median IgG4 was higher in men than women. There were positive associations of IgG subclass levels. Mean IgG1 may be lower and mean IgG2 may be higher in hemochromatosis probands than adults unselected for hemochromatosis.
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Proteína da Hemocromatose , Hemocromatose , Imunoglobulina G , Humanos , Masculino , Hemocromatose/sangue , Hemocromatose/genética , Hemocromatose/imunologia , Feminino , Imunoglobulina G/sangue , Pessoa de Meia-Idade , Proteína da Hemocromatose/genética , Adulto , Idoso , Proteínas de Membrana/imunologia , Proteínas de Membrana/genética , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologiaRESUMO
BACKGROUND: We sought to evaluate height in white adults with hemochromatosis. METHODS: We analyzed the height of (1) post-screening examination participants with HFE p.C282Y/p.C282Y (rs1800562) and wt/wt (absence of p.C282Y and p.H63D (rs1799945)) and (2) referred hemochromatosis probands with p.C282Y/p.C282Y. RESULTS: There were 762 participants (270 p.C282Y/p.C282Y, 492 wt/wt; 343 men, 419 women) and 180 probands (104 men, 76 women). Median height of male participants with p.C282Y/p.C282Y or wt/wt was 177.8 cm. Median height of female participants was greater in those with p.C282Y/p.C282Y than wt/wt (165.1 cm vs 162.6 cm, respectively; p = 0.0298). Median height of p.C282Y/p.C282Y participants and probands was the same (men 177.8 cm; women 165.1 cm). Regressions on height of male and female participants revealed no associations with HFE genotype and inverse and positive associations with age and weight, respectively. Height of female participants was positively and inversely associated with transferrin saturation and serum ferritin, respectively. Regressions on height of male and female probands revealed positive associations with weight. CONCLUSIONS: The height of men with HFE p.C282Y/p.C282Y and wt/wt does not differ significantly. The height of female participants was greater in those with p.C282Y/p.C282Y than wt/wt. We found no independent association of HFE genotype with the height of men or women.
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Estatura , Hemocromatose , População Branca , Adulto , Feminino , Humanos , Masculino , Estatura/etnologia , Estatura/genética , Ferritinas , Genótipo , Hemocromatose/diagnóstico , Hemocromatose/etnologia , Hemocromatose/genética , Proteína da Hemocromatose/genética , Antígenos de Histocompatibilidade Classe I/genética , Ferro , População Branca/genéticaRESUMO
INTRODUCTION: We sought to quantify percentages of microcytes and macrocytes in archived automated hematology analyzer (AHA) red blood cell (RBC) volume histogram images. METHODS: In preliminary studies, we demonstrated that an on-line application of Gauss' area formula (SketchAndCalc™) measured percentage areas of 20 segments under a computer-generated normal distribution curve (-3.0 standard deviations [SD] to +3.0 SD) with accuracy and precision (Pearson's correlation of measured areas with corresponding theoretical areas r [20] = 0.9962 [p < 0.0001]). Thus, we used SketchAndCalc™ to quantify percentages of microcytes (50-80 fL) and macrocytes (110-200 fL) in archived AHA histogram images in women with previously untreated iron-deficiency anemia (IDA) and previously untreated hemochromatosis. RESULTS: Median microcyte percentages in 13 women with IDA and 13 women with hemochromatosis were 63.6% (range 13.5-76.8) and 6.7% (range 3.4-24.8), respectively (p < 0.0001). Mean macrocyte percentages in women with IDA and hemochromatosis were 8.8% ± 6.1 SD and 33.8% ± 11.7 SD, respectively (p < 0.0001). Spearman's correlations of microcyte percentages with macrocyte percentages, mean corpuscular volume, and mean corpuscular hemoglobin in 26 women were rs [26] = -0.9485, rs [26] = -0.9641, and rs [26] = -0.9036, respectively (each p < 0.0001). CONCLUSIONS: This method of quantifying microcyte and macrocyte percentages could enable other studies of RBC volume subpopulations in archived AHA histogram images.
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Anemia Ferropriva , Hematologia , Hemocromatose , Humanos , Feminino , Índices de Eritrócitos , Eritrócitos AnormaisRESUMO
Our aim was to document the effects of genotype HFE p.C282Y/p.C282Y and hemochromatosis-associated laboratory and clinical manifestations on platelet counts (PC). We compiled genotype (p.C282Y/p.C282Y or HFE wt/wt (absence of p.C282Y and p.H63D (rs1799945)), age, sex, body mass index, presence/absence of chronic fatigue, swelling/tenderness of second/third metacarpophalangeal joints, and hyperpigmentation, transferrin saturation (TS), serum ferritin (SF), hemoglobin levels, absolute neutrophil, lymphocyte, and monocyte counts, C-reactive protein levels, and PC of non-Hispanic white participants in a hemochromatosis and iron overload post-screening clinical examination. There were 171 men and 254 women (141 p.C282Y/p.C282Y, 284 wt/wt) of median age 53 y. Median TS and SF were higher in p.C282Y/p.C282Y than wt/wt participants grouped by sex (p < .0001, all comparisons). Median PC by genotype was lower in men than women (p < .0001, both comparisons). Regression on PC using 14 independent variables identified these significant positive associations: absolute neutrophil, lymphocyte, and monocyte counts and C-reactive protein levels and these significant inverse associations: age, TS, and hemoglobin levels. We conclude that PC is significantly associated with absolute neutrophil, lymphocyte, and monocyte counts, and C-reactive protein (positive) and age, TS, and hemoglobin (inverse), after adjustment for other variables. HFE genotypes we studied were not significantly associated with PC.
What is the context? Hemochromatosis is typically associated with inheritance of two copies of p.C282Y, a common mutation of the HFE gene on chromosome 6p that regulates iron absorption.Platelet counts, age, and serum levels of liver enzymes have been used to estimate risks of cirrhosis in adults with hemochromatosis.Lower platelet counts in Europeans are significantly associated with a mutation in CARMIL1, a gene on chromosome 6p close to HFE.Clinical and laboratory associations of normal platelet counts in adults with HFE p.C282Y/p/C282Y and wt/wt uncomplicated by cirrhosis are unreported.What is new? We studied normal platelet counts in 425 white adults who participated in a primary care-based hemochromatosis screening program. These participants did not have cirrhosis or other conditions that often influence platelet counts.Our analyses of 14 variables identified these significant positive associations with platelet counts, after adjustment for other variables: absolute neutrophil, lymphocyte, and monocyte counts and C-reactive protein levels; and these significant inverse associations: age, TS, and hemoglobin levels.What is the impact? Laboratory and clinical factors significantly associated with platelet counts in adults with HFE p.C282/p.C282Y or wt/wt are similar to those in persons unselected for HFE genotypes or hemochromatosis.It is unlikely that genes that influence platelet counts are closely linked to HFE on chromosome 6p.Adults with hemochromatosis and HFE p.C282/p.C282Y who have abnormal platelet counts should be evaluated for cirrhosis or non-iron platelet disorders.
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Hemocromatose , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Hemocromatose/complicações , Hemocromatose/diagnóstico , Hemocromatose/genética , Proteína C-Reativa , Contagem de Plaquetas , Antígenos de Histocompatibilidade Classe I/genética , Proteína da Hemocromatose/genética , Ferritinas/genética , Genótipo , Hemoglobinas/genética , Mutação , HomozigotoRESUMO
BACKGROUND: The aim of this study was to identify characteristics of non-alcoholic fatty liver disease (NAFLD) in adults with HFE p.C282Y/p.C282Y. METHODS: We retrospectively studied non-Hispanic white hemochromatosis probands with iron overload (serum ferritin (SF) > 300 µg/L (M), > 200 µg/L (F)) and p.C282Y/p.C282Y at non-screening diagnosis who did not report alcohol consumption > 14 g/d, have cirrhosis or other non-NAFLD liver disorders, use steatogenic medication, or have diagnoses of heritable disorders that increase NAFLD risk. We identified NAFLD-associated characteristics using univariate and multivariable analyses. RESULTS: There were 66 probands (31 men, 35 women), mean age 49 ± 14 (SD) y, of whom 16 (24.2%) had NAFLD. The following characteristics were higher in probands with NAFLD: median SF (1118 µg/L (range 259, 2663) vs. 567 µg/L (247, 2385); p = 0.0192); prevalence of elevated ALT/AST (alanine/aspartate aminotransferase) (43.8% vs. 10.0%; p = 0.0056); and prevalence of type 2 diabetes (T2DM) (31.3% vs. 10.0%; p = 0.0427). Mean age, sex, and prevalences of human leukocyte antigen-A*03 positivity, body mass index ≥ 30.0 kg/m2, hyperlipidemia, hypertension, and metabolic syndrome in probands with/without NAFLD did not differ significantly. Logistic regression on NAFLD using variables SF, elevated ALT/AST, and T2DM revealed: SF (p = 0.0318; odds ratio 1.0-1.0) and T2DM (p = 0.0342; 1.1-22.3). Median iron removed to achieve iron depletion (QFe) in probands with/without NAFLD did not differ significantly (3.6 g (1.4-7.2 g) vs. 2.8 g (0.7-11.0 g), respectively; p = 0.6862). CONCLUSIONS: NAFLD in hemochromatosis probands with p.C282Y/p.C282Y is associated with higher median SF and greater T2DM prevalence, after adjustment for other factors. NAFLD does not influence QFe significantly.
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Diabetes Mellitus Tipo 2 , Hemocromatose , Sobrecarga de Ferro , Hepatopatia Gordurosa não Alcoólica , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Hemocromatose/complicações , Hemocromatose/epidemiologia , Hemocromatose/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos Retrospectivos , Antígenos de Histocompatibilidade Classe I/genética , Proteína da Hemocromatose/genética , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/epidemiologia , Ferro , HomozigotoRESUMO
BACKGROUND: Little is known about the prevalence of HFE (homeostatic iron regulator) hemochromatosis in African Americans (AA). METHODS: We defined AA as self-identified AA, blacks, or non-Hispanic blacks. We defined hemochromatosis-associated HFE genotypes as p.C282Y/p.C282Y and p.C282Y/p.H63D. We compiled prevalences of these genotypes in AA using published population and cohort data and numbers of men and women ≥18 y⬠in 2018 U.S. Census estimates. We defined iron overload (IO) and IO-related disease by genotype as previously reported in population and cohort studies of hemochromatosis in whites of European ancestry. We used these definitions to estimate prevalences and numbers of AA with IO and IO-related disease associated with hemochromatosis-associated HFE genotypes. RESULTS: There were â¼16,287,599 men and â¼17,644,898 women. HFE genotypes and their respective prevalences were: p.C282Y/p.C282Y, 0.00017 (6/34,905) [95% confidence interval 0.000034, 0.00031] and p.C282Y/p.H63D, 0.0012 (41/33,596) [0.000084, 0.0016]. IO prevalences were: men 0.000076 [0.000072, 0.000081] and women 0.0000061 [0.0000050, 0.0000073]. IO-related disease prevalences were: men 0.000063 [0.000059, 0.000067] and women 0.0000021 [0.0000014, 0.0000027]. There were â¼1021 [961, 1091] men and â¼36 [25, 48] women with IO-related disease. CONCLUSIONS: We conclude that â¼1/25,061 AA >18 y have a hemochromatosis-associated HFE genotype and IO and that â¼1/32,103 AA >18 y have a hemochromatosis-associated HFE genotype and IO-related disease.
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Hemocromatose , Sobrecarga de Ferro , Feminino , Humanos , Masculino , Negro ou Afro-Americano/genética , Genótipo , Hemocromatose/epidemiologia , Hemocromatose/genética , Proteína da Hemocromatose/genética , Antígenos de Histocompatibilidade Classe I/genética , Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/genética , Mutação , Prevalência , AdultoRESUMO
Background Characteristics of cohorts of individuals aged ≤17 years with homeostatic iron regulator (HFE) p.C282Y (rs1800562) homozygosity, a common hemochromatosis genotype, have not been reported. Methodology We retrospectively tabulated characteristics of white individuals aged ≤17 years with p.C282Y homozygosity. Individuals were not recruited for this study. We defined transferrin saturation (TS) >45%, serum ferritin (SF) >300 µg/L (M) and >200 µg/L (F) as elevated and liver iron grade 3 or 4, hepatic iron index >1.9 µmol Fe/g dry weight liver/y, and phlebotomy-mobilized iron >1.0 g (M) and >0.3 g (F) as increased. Results There were nine males and six females with a mean age of 12 ± 4 years (range = 5-17 years). The mean age of 10 probands (13 ± 3 years) was greater than that of five individuals discovered in family studies (9 ± 4 years) (p = 0.0403). Presenting manifestations of probands included fatigue/lethargy (5), elevated TS (2), and polycystic ovary syndrome, amenorrhea, and diabetes (2). In 15 individuals, the mean TS was 65 ± 23%. TS was elevated in 11 (73.3%) individuals aged 5-17 years. In 14 individuals, the mean SF was 262 ± 289 µg/L. SF was elevated and liver and phlebotomy-mobilized iron were increased in two male and three female probands aged 13-16 years (5/14 individuals, 35.7%). No individual had advanced hepatic fibrosis, arthropathy, hypogonadism, cardiomyopathy, or hyperpigmentation. Conclusions We conclude that five individuals aged 13-16 years (5/14 individuals, 35.7%) had increased liver and phlebotomy-mobilized iron.
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BACKGROUND: Screening program participants with iron overload (IO) phenotypes without HFE p.C282Y/p.C282Y are incompletely characterized. METHODS: We studied white participants who had IO phenotypes without p.C282Y/p.C282Y in post-screening clinical examinations (CE). We defined IO phenotypes as a) elevated serum ferritin (SF) and transferrin saturation (TS) at screening and CE, and b) absence of IO treatment, anemia, transfusion >10 units, alcohol intake >30 g/d, hepatitis B or C, and pregnancy. We defined IO-related disease as elevated alanine or aspartate aminotransferase (ALT/AST) or swelling/tenderness of 2nd/3rd metacarpophalangeal (MCP) joints. All participants had HFE p.C282Y and p.H63D genotyping. RESULTS: There were 32 men and 26 women (mean age 54±16 y). Median food/supplemental iron intakes were 14.3/0.0 mg/d. Relative risks of HFE genotypes were 12.9 (p.C282Y/p.H63D), 3.0 (p.H63D/p.H63D), 1.9 (p.C282Y/wt), 0.9 (p.H63D/wt), and 0.5 (wt/wt) compared to 42,640 white screening participants without IO phenotypes or p.C282Y/p.C282Y. Regression on SF revealed positive associations: MCV (p = 0.0006; ß coefficient = 0.4531); swelling/tenderness of MCP joints (p = 0.0033; ß = 0.3455); and p.H63D/wt (p = 0.0015; ß = 0.4146). IO-related disease (18 elevated ALT/AST, one swelling/tenderness of MCP joints) occurred in 19 participants (7 men, 12 women). Median MCV was higher in participants with IO-related disease (97 fL vs. 94 fL; p = 0.0007). Logistic regression on IO-related disease revealed a significant association with diabetes (p = 0.0416; odds ratio 18.9 (95% confidence interval 1.0, 341.1)). CONCLUSIONS: In the present 58 screening program participants who had IO phenotypes without HFE p.C282Y/p.C282Y, relative risks of HFE genotypes p.C282Y/p.H63D, p.H63D/p.H63D, and p.C282Y/wt were significantly higher than in 42,640 white screening participants with neither IO phenotypes nor p.C282Y/p.C282Y. SF was significantly associated with MCV, swelling/tenderness of 2nd/3rd MCP joints, and p.H63D/wt. IO-related disease was significantly associated with MCV and diabetes.
Assuntos
Hemocromatose , Sobrecarga de Ferro , Adulto , Idoso , Feminino , Ferritinas , Genótipo , Hemocromatose/complicações , Proteína da Hemocromatose/genética , Humanos , Sobrecarga de Ferro/diagnóstico , Masculino , Pessoa de Meia-Idade , Fenótipo , Transferrina/genéticaRESUMO
BACKGROUND: Human leukocyte antigen (HLA)-A*03, hemochromatosis ancestral haplotype marker, was associated with greater iron overload in hemochromatosis cohorts reported before discovery of the HFE gene. We sought to learn whether an A*03-linked locus influences phenotypes in referred HFE p.C282Y homozygotes. METHODS: We tabulated these phenotypes in probands with p.C282Y homozygosity: age, transferrin saturation (TS), serum ferritin (SF), conditions related to iron overload, fibrosis-four variables (FIB-4) index and aspartate aminotransferase-to-platelet ratio index (APRI) predictors of severe hepatic fibrosis, and iron removed to achieve depletion (QFe/age). We analyzed phenotypes of men and women separately across three A*03 subgroups. RESULTS: There were 104 men (57.8%) and 76 women (42.2%). Mean age (SD) was 49 ± 13 y. Mean TS was 79 ± 17%. Median SF (range) was 715 µg/L (28, 6103). Related conditions included: hemochromatosis arthropathy (21.7%); type 2 diabetes (18.9%); hypogonadotropic hypogonadism (5.8% of men); cardiomyopathy (0%); and cirrhosis (10.0%). Median QFe/age was 61 mg/y (0, 714). A*03 homozygosity, heterozygosity, and no A*03 occurred in 37 (20.6%), 104 (57.8%), and 39 probands (21.7%), respectively. In men, mean TS and median SF were significantly higher in A*03 homozygotes than heterozygotes but not A*03-negative probands. In men, median APRI was significantly lower in A*03 heterozygotes than homozygotes and A*03-negative probands. No other phenotypes, including QFe/age, differed significantly across A*03 subgroups in either men or women. CONCLUSIONS: Our results suggest that an A*03-linked locus does not influence phenotypes in referred HFE p.C282Y homozygotes. It is unlikely that heritable factors that modify phenotypes of p.C282Y homozygotes are linked to the hemochromatosis ancestral haplotype.
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Diabetes Mellitus Tipo 2 , Hemocromatose , Sobrecarga de Ferro , Diabetes Mellitus Tipo 2/complicações , Feminino , Antígenos HLA-A/genética , Haplótipos , Hemocromatose/genética , Proteína da Hemocromatose/genética , Antígenos de Histocompatibilidade Classe I/genética , Homozigoto , Humanos , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/genética , Proteínas de Membrana/genética , FenótipoRESUMO
Polycythemia rubra vera (PRV) is a clonal myeloproliferative neoplasm characterized by autonomous production of erythrocytes, neutrophils, and platelets. Angiomyolipomas (AMLs) are benign renal perivascular epithelioid cell neoplasms of which approximately 80% are sporadic. Here, we report synchronous diagnoses of PRV and asymptomatic sporadic bilateral renal AMLs in a 71-year-old woman. We describe her treatment with phlebotomy and hydroxyurea for PRV and surveillance for renal AMLs. We compare the features and treatment of the present case with those of two previously reported women who also had PRV and sporadic renal AMLs. Finally, we discuss the management and acquired genetic basis of both neoplasms.
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Hydroxychloroquine (HCQ) therapy decreased immunoglobulin (Ig) levels in patients with Sjögren syndrome (SS) and rheumatoid arthritis (RA) in previous studies. We found no report of Ig levels of women with IgG subclass deficiency (IgGSD) and systemic lupus erythematosus (SLE), SS, or RA treated with HCQ. We retrospectively evaluated IgG, IgG subclass, IgA, and IgM levels and other characteristics of women at IgGSD diagnosis who did and did not take HCQ for SLE, SS, or RA. There were 132 women (48 subnormal IgG1 only, 49 combined subnormal IgG1/IgG3, and 35 subnormal IgG3 only). Mean age was 49 ± 13 years. Twenty-two women with SLE, SS, RA, or combination thereof reported HCQ ≥ 200 mg/day ≥ 6 months. In each IgGSD subtype, median Ig levels of women who took HCQ were not significantly lower than those of women who did not take HCQ. Women with combined subnormal IgG1/IgG3 who took HCQ had greater median IgG2 than women who did not take HCQ (4.89 g/L (range 4.43, 4.94) vs. 2.57 g/L (1.21, 6.44), respectively; p = 0.0123). Regressions on IgG1, IgG2, and IgG3 revealed positive associations with HCQ therapy (p = 0.0043, 0.0037, and 0.0139, respectively). There were no significant Ig associations with age, SLE, SS, or RA as independent variables. HCQ therapy of SLE, SS, or RA in women with IgGSD was not associated with significantly lower IgG, IgG subclass, IgA, or IgM levels. IgG1, IgG2, and IgG3 were positively associated with HCQ therapy, after adjustment for other variables.
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Artrite Reumatoide , Deficiência de IgG , Lúpus Eritematoso Sistêmico , Síndrome de Sjogren , Adulto , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Imunoglobulina A , Imunoglobulina G , Imunoglobulina M , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Sjogren/tratamento farmacológicoRESUMO
OBJECTIVE: To describe the clinical presentation and management of a critically ill dog with profound renal tubular acidosis (RTA) with proximal and distal renal tubular dysfunction. CASE SUMMARY: A 3-year-old neutered female Border Terrier was presented with frequent regurgitation resulting from acute pancreatitis with severe ileus. Venous acid-base analysis and complete urinalysis confirmed the presence of normal anion gap metabolic acidosis with inappropriately alkaline urine (pH 8), consistent with distal RTA. Urinalysis, urine amino acids, and urinary fractional excretion of electrolytes revealed glycosuria (with normoglycemia), aminoaciduria, and increased fractional excretion of sodium, calcium, and phosphate consistent with generalized proximal renal tubulopathy or Fanconi syndrome. The dog responded well to supportive care and alkaline therapy and made a complete recovery. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first description of RTA with proximal and distal renal tubular dysfunction in the veterinary literature. Furthermore, the authors hypothesize that the transient RTA was a manifestation of acute kidney injury secondary to acute pancreatitis, the first report of this in the literature.
Assuntos
Acidose Tubular Renal , Acidose , Injúria Renal Aguda , Doenças do Cão , Pancreatite , Acidose/veterinária , Acidose Tubular Renal/complicações , Acidose Tubular Renal/diagnóstico , Acidose Tubular Renal/veterinária , Doença Aguda , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/veterinária , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/etiologia , Cães , Feminino , Pancreatite/complicações , Pancreatite/diagnóstico , Pancreatite/veterináriaRESUMO
Background: Few studies have estimated African ancestry of African Americans (AA). In sub-Saharan West African (WA) Blacks, some nonancestral alleles of iron-related genes HJV, SLC40A1, and TFR2 are common, whereas in European Americans (EA) the same alleles are rare. These alleles have not been used to estimate WA Black ancestry in AA. Methods: We estimated WA Black ancestry in AA (M) using published HJV c.929C>G (rs7540883), SLC40A1 c.744G>T (rs11568350), and TFR2 c.713C>T (rs34242818) allele frequencies in WA Blacks, AA, and EA. We computed standard error (SE) and one-sided 95% confidence intervals (CI) for each M. Results: The combined representation of WA Blacks from The Gambia and Nigeria was 79-89%. Aggregate HJV, SLC40A1, and TFR2 allele frequencies in WA Blacks were 0.1025 [95% CI: 0.0835-0.1253] (n = 405), 0.0517 [0.0469-0.0569] (n = 3839), and 0.1432 [0.1202-0.1697] (n = 405), respectively. Aggregate HJV, SLC40A1, and TFR2 allele frequencies in AA were 0.0718 [0.0648-0.0797] (n = 2352), 0.0557 [0.0506-0.0613] (n = 3590), and 0.1224 [0.1132-0.1322] (n = 2352), respectively. Aggregate HJV, SLC40A1, and TFR2 allele frequencies in 4449 EA were 0.0002 [0-0.0009], 0.0003 [0.0001-0.0010], and 0.0004 [0.0001-0.0012], respectively. M (SE [one-sided 95% CI]) for HJV, SLC40A1, and TFR2 alleles was 0.7006 (0.0818 [0.5402-1.0000]), 1.0000 (0.0752 [0.9306-1.0000]), and 0.8546 (0.0810 [0.6959-1.0000]), respectively. Mean of these M is 0.8777 (87.8%). Conclusions: The mean proportional WA Black ancestry in AA of 87.8% using HJV c.929C>G, SLC40A1 c.744G>T, and TFR2 c.713C>T allele frequencies is consistent with that of previous studies that used other autosomal markers and methods.
Assuntos
Negro ou Afro-Americano , Proteínas de Transporte de Cátions , Proteínas Ligadas por GPI , Proteína da Hemocromatose , Ferro , Receptores da Transferrina , Negro ou Afro-Americano/genética , Alelos , População Negra/genética , Proteínas de Transporte de Cátions/genética , Proteínas Ligadas por GPI/genética , Frequência do Gene , Genética Populacional , Proteína da Hemocromatose/genética , Humanos , Receptores da Transferrina/genéticaRESUMO
OBJECTIVE: To perform a retrospective, multicenter observational study that compares the agreement of rectal temperature with the temperature measured with noncontact infrared thermometer (NCIT) in a population of dogs and cats. Animals: 168 dogs and 61 cats. PROCEDURES: NCIT readings were taken in triplicate from the medial pinna, then rectal temperature was taken with a standard digital rectal thermometer (RT). Ambient room temperature, signalment, presence of icterus, skin and coat color, reason for presentation, and final diagnosis were recorded. RESULTS: In dogs, median (range) body temperature reflected by RT and NCIT measurements was 38.4 °C (33.4 to 40.3 °C) and 36.3 °C (30.8 to 40.0 °C), respectively. In cats, median (range) body temperature reflected by RT and NCIT measurements was 38.3 °C (36.2 to 40.0 °C) and 35.7 °C (31.8 to 38.0 °C), respectively. There was a weak positive correlation between body temperatures measured by NCIT and RT in dogs (Kendall tau = 0.154), but there was no correlation in cats (Kendall tau = -0.01). A significant, albeit weak, agreement was seen between temperature measured by NCIT and RT in dogs (Kappa value, 0.05), but not cats (Kappa value, -0.08). In both species, NCIT tended to underread body temperature, compared with RT (dogs: mean ± SD bias -2.2 ± 1.51 °C; cats: mean bias -2.7 ± 1.44 °C), with the degree of low measurements lessening as body temperature increased. CLINICAL RELEVANCE: Given both poor correlation and agreement in body temperature measured by NCIT and rectal thermometer, NCIT measurements cannot be recommended at the current time as a means to determine body temperature in dogs and cats.
Assuntos
Doenças do Gato , Doenças do Cão , Animais , Temperatura Corporal , Doenças do Gato/diagnóstico , Gatos , Cães , Reto , Estudos Retrospectivos , Temperatura , Termômetros/veterináriaRESUMO
BACKGROUND: In hemochromatosis, causes of abdominal pain and its associations with cirrhosis are poorly understood. METHODS: We retrospectively compared characteristics of referred hemochromatosis probands with HFE p.C282Y homozygosity with/without biopsy-proven cirrhosis: sex, age, diabetes, heavy alcohol consumption, abdominal pain/tenderness, hepatomegaly, splenomegaly, non-alcoholic fatty liver disease, chronic viral hepatitis, ascites, transferrin saturation (TS), serum ferritin (SF), and iron removed by phlebotomy (QFe). We performed logistic regression on cirrhosis using characteristics identified in univariate comparisons. We performed computerized and manual searches to identify hemochromatosis case series and compiled prevalence data on cirrhosis and abdominal pain and causes of abdominal pain. RESULTS: Of 219 probands, 57.1% were men. Mean age was 48±13 y. In 22 probands with cirrhosis, proportions of men, mean age, prevalences of heavy alcohol consumption, abdominal pain, abdominal tenderness, hepatomegaly, splenomegaly, and chronic viral hepatitis, and median TS, SF, and QFe were significantly greater than in probands without cirrhosis. Regression analysis revealed three associations with cirrhosis: abdominal pain (p = 0.0292; odds ratio 9.8 (95% CI: 1.2, 76.9)); chronic viral hepatitis (p = 0.0153; 11.5 (95% CI: 1.6, 83.3)); and QFe (p = 0.0009; 1.2 (95% CI: 1.1, 1.3)). Of eight probands with abdominal pain, five had cirrhosis and four had diabetes. One proband each with abdominal pain had heavy alcohol consumption, chronic viral hepatitis B, hepatic sarcoidosis, hepatocellular carcinoma, and chronic cholecystitis, cholelithiasis, and sigmoid diverticulitis. Abdominal pain was alleviated after phlebotomy alone in four probands. In 12 previous reports (1935-2011), there was a negative correlation of cirrhosis prevalence and publication year (p = 0.0033). In 11 previous reports (1935-1996), a positive association of abdominal pain prevalence and publication year was not significant (p = 0.0802). CONCLUSIONS: Abdominal pain, chronic viral hepatitis, and QFe are significantly associated with cirrhosis in referred hemochromatosis probands with HFE p.C282Y homozygosity. Iron-related and non-iron-related factors contribute to the occurrence of abdominal pain.
Assuntos
Dor Abdominal/etiologia , Proteína da Hemocromatose/genética , Hemocromatose/complicações , Cirrose Hepática/etiologia , Feminino , Hemocromatose/genética , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Estudos RetrospectivosRESUMO
BACKGROUND: Factors associated with IgG levels in adults with IgG subclass deficiency (IgGSD) are incompletely understood. We studied adults with IgGSD with subnormal IgG1 only, subnormal IgG1/IgG3, or subnormal IgG3 only without other subnormal IgG subclasses, IgA, or IgM. We compiled: age; sex; autoimmune condition(s) (AC); atopy; IgG, IgG subclasses, IgA, IgM; IgGsum (IgG1 + IgG2 + IgG3 + IgG4); and D (percentage difference between IgGsum and IgG). We compared attributes of patients with/without subnormal IgG (< 7.00 g/L; subnormal IgG1 subclass groups only) and analyzed IgGsum and IgG relationships. We performed backward stepwise regressions on IgG using independent variables IgG subclasses, age, and sex and on D using independent variables age and sex. RESULTS: There were 39 patients with subnormal IgG1 only (89.7% women), 53 with subnormal IgG1/IgG3 (88.7% women), and 115 with subnormal IgG3 only (91.3% women). Fifteen patients (38.5%) and 32 patients (60.4%) in the respective subnormal IgG1 subclass groups had subnormal IgG. Attributes of patients with/without IgG < 7.00 g/L were similar, except that AC prevalence was lower in patients with subnormal IgG1 only and IgG < 7.00 g/L than ≥ 7.00 g/L (p = 0.0484). Mean/median IgG1 and IgG2 were significantly lower in patients with IgG < 7.00 g/L in both subnormal IgG1 subclass groups (p < 0.0001, all comparisons). Regressions on IgG in three subclass groups revealed positive associations with IgG1 and IgG2 (p < 0.0001 each association). Regressions on D revealed no significant association. IgG1 percentages of IgGsum were lower and IgG2 percentages were higher in patients with subnormal IgG1 subclass levels than subnormal IgG3 only (p < 0.0001 all comparisons). CONCLUSIONS: We conclude that both IgG1 and IgG2 are major determinants of IgG in patients with subnormal IgG1, combined subnormal IgG1/IgG3, or subnormal IgG3 and that in patients with subnormal IgG1 or combined subnormal IgG1/IgG3, median IgG2 levels are significantly lower in those with IgG < 7.00 g/L than those with IgG ≥ 7.00 g/L.
Assuntos
Doenças Autoimunes/imunologia , Deficiência de IgG/imunologia , Imunoglobulina G/genética , Isotipos de Imunoglobulinas/genética , Adulto , Idoso , Doenças Autoimunes/epidemiologia , Feminino , Humanos , Deficiência de IgG/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Adults with IgG subclass deficiency (IgGSD) with subnormal IgG2 are inadequately characterized. METHODS: We retrospectively analyzed observations in unrelated adults with IgGSD evaluated in a single hematology clinic (1991-2019) and selected those with subnormal serum IgG2 (<117 mg/dL (<1.2 g/L)) without corticosteroid therapy to describe: age; prevalence of women; upper/lower respiratory infection; autoimmune condition(s); atopy; other allergy; frequent or severe respiratory tract infection in first-degree relatives; IgG, IgG subclasses, IgA, and IgM; blood lymphocyte subpopulations; human leukocyte antigen (HLA)-A and -B types and haplotypes; and 23-valent pneumococcal polysaccharide vaccination (PPSV23) responses. We determined the prevalence of subnormal IgG2 among unrelated adults with IgGSD without corticosteroid therapy and compared general characteristics of those with and without subnormal IgG2. RESULTS: There were 18 patients (94.4% women) with subnormal IgG2. Mean age was 52 ± 11 y. Upper/lower respiratory infection occurred in 94.4%/74.8%, respectively. Autoimmune condition(s), atopy, other allergy, and frequent or severe respiratory infection in first-degree relatives occurred in 44.4%, 44.4%, 61.1%, and 22.2%, respectively. Median IgG2 was 105 mg/dL (83, 116). Subnormal IgG, IgG1, IgG3, IgG4, IgA, and IgM was observed in 66.7%, 50.0%, 100.0%, 5.6%, 33.3%, and 0%, respectively. Lymphocyte subpopulations were normal in most patients. HLA frequencies were similar in patients and controls. Three of 4 patients had no protective S. pneumoniae serotype-specific IgG levels before or after PPSV23. These 18 patients represent 7.6% of 236 adults with IgGSD. Prevalence of subnormal IgG, subnormal IgG3, and subnormal IgA was significantly greater in 18 adults with subnormal IgG2 than 218 adults without subnormal IgG2. Prevalence of subnormal IgM was significantly lower in patients with subnormal IgG2. CONCLUSIONS: Characteristics of adults with IgGSD with subnormal IgG2 include female predominance, other immunologic abnormalities, subnormal IgG3 and/or IgG1, lack of HLA-A and -B association, and suboptimal PPSV23 response.
Assuntos
Biomarcadores/sangue , Deficiência de IgG/epidemiologia , Imunoglobulina G/sangue , Infecções Respiratórias/epidemiologia , Adulto , Feminino , Seguimentos , Antígenos HLA/metabolismo , Humanos , Deficiência de IgG/sangue , Deficiência de IgG/patologia , Incidência , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Infecções Respiratórias/sangue , Infecções Respiratórias/patologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Background: HFE p.C282Y (chromosome 6p22.2; exon 4, c.845G>A; rs1800562), a hemochromatosis-associated polymorphism in European Americans, is absent in sub-Saharan West African blacks. Methods: We estimated European American ancestry in African Americans (M) using published p.C282Y allele frequencies of sub-Saharan West African blacks; and ≥50 unselected African Americans and ≥50 unselected European Americans in the same city/region. Results: p.C282Y allele frequency in 870 West African blacks (The Gambia, Ghana, Nigeria, Senegal, Sierra Leone) was 0.0000 (confidence interval [95% CI 0.0000-0.0027]). p.C282Y allele frequencies in European Americans were 0.0600 (12,592 participants; five single-site studies) and 0.0673 (54,882 participants; two multisite studies). p.C282Y allele frequencies in African Americans were 0.0102 (3084 participants; five single-site studies) and 0.0122 (30,762 participants; two multisite studies). M for all data was 0.1803 (standard error 0.0049; [95% CI 0.1706-0.1900]). City/region estimates of M differed 1.8-fold: 0.1321, Rochester, NY; 0.1456, Birmingham, AL; 0.1569, Upper Savannah Region, SC; 0.1612, Portland, OR; 0.1746, San Diego, CA; 0.1780, Hartford, CT; 0.1957, District of Columbia; 0.2377, Oakland, CA; and 0.2429, Irvine, CA. Conclusions: Estimates of M using p.C282Y are consistent with those using other autosomal markers, differ across nine cities/regions, and reflect paternal and maternal contributions of European American ancestry in African Americans.
Assuntos
Negro ou Afro-Americano/genética , Proteína da Hemocromatose/genética , Alelos , População Negra/genética , Feminino , Frequência do Gene/genética , Genótipo , Proteína da Hemocromatose/metabolismo , Humanos , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Estados Unidos , População Branca/genéticaRESUMO
Subnormal IgG1 or IgG3 levels occurred in 30% of hemochromatosis probands with HFE p.C282Y homozygosity and were concordant in HLA-identical siblings. We sought to identify factors associated with IgG subclasses in Alabama probands with p.C282Y homozygosity evaluated for 500â¯kb microhaplotypes AAT and GGG defined by SNPs in chromosome 6p genes PGBD1, ZNF193, and ZNF165. In regressions on IgG subclasses, we used: age; sex; GGG (dichotomous); iron removed to achieve depletion; CD8+ T-lymphocytes; and other IgG subclasses. Among 49 probands, AAT and GGG occurred in 95.9% and 16.3%, respectively. Thirteen probands (26.5%) had subnormal IgG1; 11 probands (22.4%) had subnormal IgG3. Mean IgG3 was higher in probands with than without GGG (75â¯mg/dL [95% confidence interval 63, 89] vs. 58â¯mg/dL [49, 71], respectively; pâ¯=â¯0.0321). Regression on IgG3 revealed: GGG positivity (pâ¯=â¯0.0106); and IgG1 (pâ¯=â¯0.0015). In a replication cohort of 22 Portugal probands with p.C282Y homozygosity, mean IgG3 was higher in probands with than without GGG (46⯱â¯16 vs. 31⯱â¯12â¯mg/dL, respectively; pâ¯=â¯0.0410). We conclude that mean IgG3 levels are higher in hemochromatosis probands with p.C282Y homozygosity with chromosome 6p microhaplotype GGG than in probands homozygous for microhaplotype AAT.