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1.
Arch Immunol Ther Exp (Warsz) ; 68(3): 14, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32307610

RESUMO

We sought to determine whether HLA-A and -B type and haplotype frequencies differ between subgroups of adults with IgG subclass deficiency (IgGSD). We retrospectively compared type and haplotype frequencies of three subgroups of 269 unrelated adult IgGSD patients (70 subnormal IgG1; 121 subnormal IgG3; 78 subnormal IgG1/IgG3) and controls (1,321 for types; 751 for haplotypes). We selected types and haplotypes because their uncorrected frequencies differed significantly from controls in a previous adult IgGSD/common variable immunodeficiency cohort: A*24; B*14; B*35; B*40; B*49; B*50; B*58; B*62; A*01,B*08; A*02,B*44; A*02,B*60; A*03,B*07; A*03,B*14; A*03,B*44; A*31,B*40; and A*32,B*14. We used χ2 analysis (2 × 4 tables) to identify frequency differences across three subgroups and controls. If the null hypothesis was rejected (p < 0.05), we computed 2 × 2 χ2 tables to compare six combinations of subgroup and control frequencies [Bonferroni p < 0.0083 (< 0.05/6)]. Mean age was 48 ± 13 years; 82.2% were women. B*35 and B*40 frequencies were higher in subnormal IgG1 than subnormal IgG3 patients (0.1000 vs. 0.0248 and 0.0571 vs. 0.0083, respectively; p ≤ 0.0061). B*62 frequencies were lower in three IgGSD subgroups than controls (p < 0.0001, respectively). A*02, B*44 frequency was higher in subnormal IgG1/IgG3 patients than controls (0.1282 vs. 0.0632, respectively; p = 0.0024). A*02, B*60 frequency was lower in subnormal IgG3 patients than controls (0.0 vs. 0.0233, respectively; p = 0.0051). HLA-B*35 and -B*40 frequencies differ significantly between some IgGSD subgroups. B*62, A*02, B*44, and A*02, B*60 frequencies differ significantly between some IgGSD subgroups and controls.

2.
BMC Immunol ; 20(1): 29, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429700

RESUMO

BACKGROUND: We sought to compare Pneumovax®23 responses in adults with subnormal IgG subclass concentrations. We studied adults with normal total IgG, frequent/severe respiratory infection, and subnormal IgG1, IgG3, or IgG1 + IgG3 before and after Pneumovax®23. We defined response as serotype-specific IgG > 1.3 µg/mL and aggregate response as IgG > 1.3 µg/mL for ≥70% of all serotypes tested. We compared patients with and without serotype-specific responses and performed logistic regression on aggregate responses using: age; male sex; body mass index; autoimmune condition(s); atopy; other allergies; subnormal IgGSc immunophenotypes; IgA; and IgM. RESULTS: There were 59 patients (mean age 44 ± 13 (SD) years; 83.1% women). Median days between pre- and post-Pneumovax®23 testing was 33 (range 19-158). The median post-vaccination summated concentration of serotype-specific IgG was higher in patients with subnormal IgG1 than subnormal IgG3 (responders and non-responders). All subnormal IgG1 + IgG3 non-responders responded to serotypes 8, 9 and 26, unlike other non-responders. Subnormal IgG3 responders had lower responses to serotypes 1, 4, 12, 23, 26, and 51. Subnormal IgG3 non-responders had higher responses to serotypes 1, 3, 8, 9, 12, 14, 19, 51, and 56. Response rates decreased with increasing age. Aggregate responders were: subnormal IgG1, 54%; IgG3, 46%; and IgG1 + IgG3, 46%. Regression on aggregate response revealed lower response with male sex (odds ratio 0.09 [95% CI 0.01, 0.77]) and atopy (0.17 [0.03, 0.83]). CONCLUSIONS: Serotype-specific IgG responses to Pneumovax®23 were greater in patients with subnormal IgG1 than subnormal IgG3. Male sex and atopy were associated with lower aggregate responses.


Assuntos
Anticorpos Antibacterianos/imunologia , Imunoglobulina G/imunologia , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Vacinação , Adulto , Aglutinação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Sorogrupo , Streptococcus pneumoniae/classificação
3.
BMC Immunol ; 20(1): 15, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31117958

RESUMO

BACKGROUND: Mannose-binding lectin (MBL) deficiency may increase risk of respiratory tract infection in adults unselected for IgG or IgG subclass levels. In a retrospective study, we sought to determine associations of serum MBL levels with clinical and laboratory characteristics of unrelated non-Hispanic white adults at diagnosis of IgG subclass deficiency (IgGSD). We computed the correlation of first and second MBL levels expressed as natural logarithms (ln) in a patient subgroup. We compared these characteristics of all adults with and without MBL ≤50 ng/mL: age; sex; body mass index; upper/lower respiratory tract infection; diabetes; autoimmune condition(s); atopy; other allergy; corticosteroid therapy; and subnormal serum IgG subclasses, IgA, and IgM. We performed logistic regression on MBL ≤50 ng/mL (dichotomous) using the three independent variables with the lowest values of p in univariate comparisons. RESULTS: There were 219 patients (mean age 51 ± 13 y; 82.5% women). Thirty-six patients (16.4%) had MBL ≤50 ng/mL. Two MBL measurements were available in 14 patients. The median interval between the first and second measurements was 125 d (range 18-1031). For ln-transformed data, we observed adjusted r2 = 0.9675; Pearson correlation coefficient 0.9849; and p < 0.0001. Characteristics of patients with and without MBL ≤50 ng/mL did not differ significantly in univariate comparisons. We performed a regression on MBL ≤50 ng/mL using: subnormal IgM (p = 0.0565); upper respiratory tract infection (p = 0.1094); and body mass index (p = 0.1865). This regression revealed no significant associations. CONCLUSIONS: We conclude that the proportion of the present IgGSD patients with serum MBL ≤50 ng/mL is similar to that of healthy European adults. MBL ≤50 ng/mL was not significantly associated with independent variables we studied.


Assuntos
Doenças Autoimunes/epidemiologia , Deficiência de IgG/epidemiologia , Imunoglobulina G/genética , Lectina de Ligação a Manose/sangue , Lectina de Ligação a Manose/deficiência , Erros Inatos do Metabolismo/epidemiologia , Infecções Respiratórias/epidemiologia , Adulto , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Risco , Estados Unidos/epidemiologia
4.
Blood Cells Mol Dis ; 77: 72-75, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30986649

RESUMO

Few case series of pagophagia and iron deficiency include men. We performed a retrospective study of non-Hispanic white men with iron-deficiency anemia whose anemia and pagophagia, thrombocytosis, and thrombocytopenia (if present) resolved after iron replacement. Iron-deficiency anemia was defined as transferrin saturation (TS) <15%, serum ferritin (SF) <30 µg/L, and hemoglobin (Hb) <13.0 g/dL. We excluded men with: anemia, thrombocytosis, or thrombocytopenia due to non-iron-deficiency causes; malignancy; chronic inflammatory conditions; hemochromatosis; or creatinine >1.1 mg/dL. We computed univariate and multivariable pagophagia associations with: age; gastrointestinal bleeding; TS; SF; Hb; red blood cell (RBC) count; mean corpuscular volume (MCV); RBC distribution width (RDW); and platelet count. Median age of 41 men was 54 y (range 18-81). Fourteen men (34.1%) had pagophagia. Thirty-six men (87.8%) had gastrointestinal bleeding. Mean Hb was 9.4 ±â€¯2.2 g/dL. Six men (14.6%) had thrombocytosis; two (4.9%) had thrombocytopenia. Logistic regression on pagophagia revealed: age (p = 0.0158; odds ratio 0.92 [95% confidence interval: 0.85, 0.99]) and platelet count (p = 0.0187; 0.98 [0.97, 1.00]) (41.4% of pagophagia occurrence; ANOVA p = 0.0053). We conclude that pagophagia occurred in 34% of men with iron-deficiency anemia and was negatively associated with age and platelet count, after adjustment for other variables.


Assuntos
Anemia Ferropriva/complicações , Pica/diagnóstico , Pica/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/terapia , Índices de Eritrócitos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Avaliação de Sintomas , Adulto Jovem
5.
J Vasc Access ; 19(4): 375-377, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29542377

RESUMO

BACKGROUND: We sought to learn more about the utility and safety of implanted ports for monthly immunoglobulin G infusions in adults with primary immune deficiency. METHODS: We reviewed charts of adults who were referred to a single practice during the interval 2006-2016 for evaluation and management of frequent or severe upper and lower respiratory tract and other infections, subnormal total immunoglobulin G or immunoglobulin G subclasses, and suboptimal responses to polyvalent pneumococcal polysaccharide vaccinations; were diagnosed to have primary immune deficiency; and were advised to undergo immunoglobulin G therapy. RESULTS: Of 606 patients, 20 (19 women, 1 man; 16 immunoglobulin G subclass deficiency, 4 common variable immunodeficiency; 3.3%) needed implanted ports because they had inadequate upper extremity superficial venous access. Median age at diagnosis was 48 years (range: 32-65 years). In total, 17 of the 20 patients preferred monthly in-office intravenous immunoglobulin G treatment to weekly at-home subcutaneous immunoglobulin G. The other three patients could not be treated with subcutaneous immunoglobulin G (unfavorable self-treatment experiences and insurance limitations). Median duration of treatment via implanted ports was 73 months (range: 10-153 months). In the man, the first implanted port was replaced after 26 months due to catheter fracture of unknown cause. His second port has been used for 112 months. We observed no other port-related failure, infections, thrombosis, or other adverse events. CONCLUSION: The utility and safety of implanted ports in adults with primary immune deficiency for whom subcutaneous immunoglobulin G therapy is not desired or feasible are probably similar to those of ports in patients without primary immune deficiency.


Assuntos
Cateterismo Venoso Central/instrumentação , Cateteres de Demora , Cateteres Venosos Centrais , Imunoglobulina G/administração & dosagem , Síndromes de Imunodeficiência/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Adulto , Idoso , Cateterismo Venoso Central/efeitos adversos , Esquema de Medicação , Falha de Equipamento , Feminino , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/imunologia , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Preferência do Paciente , Fatores de Tempo , Resultado do Tratamento
7.
Curr Top Microbiol Immunol ; 408: 25-45, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28702710

RESUMO

Since the bona fide Fc receptor for IgM antibody (FcµR) was identified eight years ago, much progress has been made in defining its biochemical nature, cellular distribution, and effector function. However, there are clearly conflicting results, especially about the cellular distribution and function of murine FcµR. In this short article, we will discuss recent findings from us and other investigators along with our interpretations and comments that may help to resolve the existing puzzles and should open new avenues of investigation.


Assuntos
Imunoglobulina M/imunologia , Imunoglobulina M/metabolismo , Receptores Fc/imunologia , Receptores Fc/metabolismo , Animais
8.
Case Rep Gastroenterol ; 11(2): 293-304, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28626375

RESUMO

Intravenous bevacizumab decreased mucosal bleeding in some patients with hereditary hemorrhagic telangiectasia (HHT). We treated a 47-year-old male who had HHT, severe epistaxis, and gastrointestinal bleeding, alcoholic cirrhosis, and portal hypertension with intravenous bevacizumab 2.5 mg/kg every 2 weeks. We tabulated these measures weekly during weeks 1-33 (no bevacizumab); 34-57 (bevacizumab); and 58-97 (no bevacizumab): hemoglobin (Hb) levels; platelet counts; units of transfused packed erythrocytes (PRBC units); and quantities of iron infused as iron dextran to support erythropoiesis. We performed univariate and multivariable analyses. We sequenced his ENG and ACVRL1 genes. Epistaxis and melena decreased markedly during bevacizumab treatment. He reported no adverse effects due to bevacizumab. Mean weekly Hb levels were significantly higher and mean weekly PRBC units and quantities of intravenous iron were significantly lower during bevacizumab treatment. We performed a multiple regression on weekly Hb levels using these independent variables: bevacizumab treatment (dichotomous); weekly platelet counts; weekly PRBC units; and weekly quantities of intravenous iron. There was 1 positive association: (bevacizumab treatment; p = 0.0046) and 1 negative association (PRBC units; p = 0.0004). This patient had the novel ENG mutation E137K (exon 4; c.409G→A). Intravenous bevacizumab treatment 2.5 mg/kg every 2 weeks for 24 weeks was well-tolerated by a patient with HHT due to ENG E137K and was associated with higher weekly Hb levels and fewer weekly PRBC units.

9.
Clin Exp Rheumatol ; 35 Suppl 105(3): 68-73, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28422000

RESUMO

OBJECTIVES: We sought to determine the prevalence and clinical and laboratory associations of fibromyalgia in adults with primary immunodeficiency (immunoglobulin (Ig) G subclass deficiency (IgGSD) and common variable immunodeficiency (CVID). METHODS: We performed a retrospective analysis of these observations in 300 non-Hispanic white adult index patients with recurrent/severe respiratory tract infections and IgGSD or CVID: age; sex; IgGSD; fibromyalgia; chronic fatigue; autoimmune conditions (ACs); interstitial cystitis (IC); diabetes; body mass index; serum Ig isotypes; blood lymphocytes and subsets; and human leukocyte antigen (HLA)-A and -B types and haplotypes. We performed univariate comparisons, logistic multivariable regressions, and an analysis of covariance. RESULTS: Mean age was 49 ± 12 (standard deviation) y. There were 246 women (82.0%). IgGSD was diagnosed in 276 patients (92.0%). Fifty-six patients had fibromyalgia (18.7%; female:male 13:1). Other characteristics included: chronic fatigue, 63.0%; aggregate ACs, 35.3%; Sjögren's syndrome, 8.0%; IC, 3.0%; diabetes, 10.3%; and HLA-A*29, B*44 positivity, 9.7%. Prevalences of female sex; chronic fatigue; IC; and HLA-A*29, B*44 positivity were greater in patients with fibromyalgia. Logistic regression on fibromyalgia revealed three positive associations: chronic fatigue (p=0.0149; odds ratio 2.6 [95% confidence interval 1.2, 5.6]); Sjögren's syndrome (p=0.0004; 5.2 [2.1, 13.2]); and IC (p=0.0232; 5.7 [1.3, 25.7]). In an analysis of covariance, there were significant interactions of chronic fatigue, Sjögren's syndrome, and interstitial cystitis on fibromyalgia. CONCLUSIONS: Fibromyalgia is common in non-Hispanic white adult index patients with primary immunodeficiency, especially women. Chronic fatigue, Sjögren's syndrome, and IC are significantly associated with fibromyalgia after adjustment for other independent variables.


Assuntos
Imunodeficiência de Variável Comum/epidemiologia , Fibromialgia/epidemiologia , Deficiência de IgG/epidemiologia , Síndrome de Sjogren/epidemiologia , Adulto , Doenças Autoimunes/epidemiologia , Imunodeficiência de Variável Comum/genética , Cistite Intersticial/epidemiologia , Síndrome de Fadiga Crônica/epidemiologia , Feminino , Fibromialgia/genética , Antígenos HLA-A/genética , Antígeno HLA-B44/genética , Haplótipos , Humanos , Deficiência de IgG/genética , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/genética , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Estudos Retrospectivos
10.
J Immunol Res ; 2016: 1405950, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27123464

RESUMO

We characterized 54 adult index patients with reports of frequent or severe bacterial respiratory tract infections at diagnosis of selective subnormal IgG1. Mean age was 50 ± 13 (SD) y; 87.0% were women. Associated disorders included the following: autoimmune conditions 50.0%; hypothyroidism 24.1%; atopy 38.9%; and other allergy 31.5%. In 35.5%, proportions of protective S. pneumoniae serotype-specific IgG levels did not increase after polyvalent pneumococcal polysaccharide vaccination (PPPV). Blood lymphocyte subset levels were within reference limits in most patients. Regressions on IgG1 and IgG3 revealed no significant association with age, sex, autoimmune conditions, hypothyroidism, atopy, other allergy, corticosteroid therapy, or lymphocyte subsets. Regression on IgG2 revealed significant associations with PPPV response (negative) and CD19+ lymphocytes (positive). Regression on IgG4 revealed significant positive associations with episodic corticosteroid use and IgA. Regression on IgA revealed positive associations with IgG2 and IgG4. Regression on IgM revealed negative associations with CD56+/CD16+ lymphocytes. Regressions on categories of infection revealed a negative association of urinary tract infections and IgG1. HLA-A(⁎)03, HLA-B(⁎)55 and HLA-A(⁎)24, HLA-B(⁎)35 haplotype frequencies were greater in 38 patients than 751 controls. We conclude that nonprotective S. pneumoniae IgG levels and atopy contribute to increased susceptibility to respiratory tract infections in patients with selective subnormal IgG1.


Assuntos
Deficiência de IgG/imunologia , Imunoglobulina G/sangue , Infecções Respiratórias/imunologia , Streptococcus pneumoniae/imunologia , Doença Aguda , Adulto , Idoso , Antígenos CD19/imunologia , Doenças Autoimunes/complicações , Doenças Autoimunes/imunologia , Suscetibilidade a Doenças , Feminino , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Haplótipos , Humanos , Hipersensibilidade/complicações , Hipersensibilidade/imunologia , Hipotireoidismo/complicações , Hipotireoidismo/imunologia , Deficiência de IgG/complicações , Imunoglobulina A/sangue , Imunoglobulina M/sangue , Subpopulações de Linfócitos , Masculino , Pessoa de Meia-Idade , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/efeitos adversos , Infecções Respiratórias/complicações , Infecções Respiratórias/genética , Infecções Respiratórias/microbiologia , Estudos Retrospectivos , Infecções Urinárias/imunologia
11.
Case Rep Med ; 2016: 8159302, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26880930

RESUMO

Reports of pica for uncooked rice (ryzophagia) in adults who reside in European and derivative countries are uncommon. We evaluated and treated two nonpregnant women with pica for uncooked basmati rice. Both women reported fatigue, abdominal discomfort after consuming large quantities of uncooked basmati rice, and hair loss. One woman was from India and the other was from Pakistan. Both women were vegetarians. Basmati was the local rice in their native countries and their usual rice in the USA. Both women had tooth damage due to eating uncooked rice and iron deficiency with microcytic anemia attributed to menorrhagia and multiparity. Ryzophagia and other manifestations (except tooth damage) resolved after iron dextran therapy. We review and discuss other reports of ryzophagia associated with iron deficiency, pregnancy, race/ethnicity, geographic origin, and local traditions. We conclude that adults with ryzophagia in European and derivative countries are likely to be non-Europeans.

12.
Cell Immunol ; 299: 50-7, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26410396

RESUMO

We characterized 121 adults with frequent or severe bacterial respiratory tract infections at diagnosis of selective subnormal IgG3. Mean age was 47 ± 13 (SD)y; 87.6% were women. Associated disorders included: autoimmune conditions 33.1%; hypothyroidism 14.9%; atopy 29.8%; and other allergy manifestations 41.3%. In 34.1%, proportions of protective Streptococcus pneumoniae serotype-specific IgG levels did not increase after polyvalent pneumococcal polysaccharide vaccination. Blood CD19+, CD3+/CD4+, CD3+/CD8+, and CD56+/CD16+ lymphocyte levels were within reference limits in most patients. In regression analyses, independent variables age; sex; autoimmune conditions; hypothyroidism; atopy; allergy manifestations; corticosteroid therapy; and lymphocyte subsets were not significantly associated with IgG subclass, IgA, or IgM levels. Frequencies of HLA haplotypes A*01, B*08; A*02, B*14; A*02, B*15; A*02, B*44; A*02, B*57; and A*03, B*07 were greater in 80 patients than 751 controls. We conclude that subnormal IgG3 and non-protective S. pneumoniae IgG levels contribute to increased susceptibility to respiratory tract infections.


Assuntos
Infecções Bacterianas/sangue , Infecções Bacterianas/imunologia , Suscetibilidade a Doenças/imunologia , Imunoglobulina G/sangue , Infecções Respiratórias/sangue , Infecções Respiratórias/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Am J Med Sci ; 349(1): 50-5, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25559280

RESUMO

BACKGROUND: Primary iron overload in African Americans has been reported predominantly from autopsy studies. METHODS: We characterized hepatic iron phenotypes in 83 African Americans who underwent liver biopsy during the interval 1990 to 1995. We tabulated pathology report form data, iron grades in hepatocytes (0-4) and Kupffer cells (0-3) and abnormal liver histology. Increased iron was defined as hepatocyte or Kupffer iron grades ≥ 2, respectively. Heavy iron was defined as hepatocyte iron grade 3 or 4. Primary iron overload was defined as the presence of grade 3 or 4 hepatocellular iron in the absence of evidence of chronic alcohol effect, viral hepatitis, steatosis, unexplained inflammation, chronic erythrocyte transfusion or chronic ingestion of iron supplements. RESULTS: There were 37 men and 46 women (mean age: 53 ± 15 [SD] years). We observed heavy ethanol consumption, 12.0%; viral hepatitis, 26.5%; steatosis without heavy ethanol consumption, 43.4%; inflammation, 45.6%; fibrosis, 26.2% and bridging fibrosis/cirrhosis, 29.4%. Logistic regression on bridging fibrosis/cirrhosis revealed positive associations with heavy ethanol consumption (P = 0.0410) and viral hepatitis (P = 0.0044). The 22 patients (26.5%) with increased iron had greater mean age, proportion of men and heavy ethanol consumption. Five patients had heavy iron staining, among whom were 3 women (mean age: 54 years) with primary iron overload. Two of the 3 women had cirrhosis and diabetes mellitus. CONCLUSIONS: Among 83 adult African Americans who underwent liver biopsy, 3.6% had hepatic iron phenotypes consistent with primary iron overload.


Assuntos
Afro-Americanos , Sobrecarga de Ferro , Ferro/metabolismo , Hepatopatias , Fígado/metabolismo , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/etnologia , Consumo de Bebidas Alcoólicas/metabolismo , Biópsia , Feminino , Hepatócitos/metabolismo , Humanos , Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/etnologia , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Macrófagos do Fígado/metabolismo , Fígado/patologia , Hepatopatias/epidemiologia , Hepatopatias/etnologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Pessoa de Meia-Idade
14.
J Immunol Res ; 2014: 542706, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25295286

RESUMO

Common variable immunodeficiency (CVID) and immunoglobulin (Ig) G subclass deficiency (IgGSD) are heterogeneous disorders characterized by respiratory tract infections, selective Ig isotype deficiencies, and impaired antibody responses to polysaccharide antigens. Using univariable analyses, we compared observations in 34 CVID and 398 IgGSD adult index patients (81.9% women) referred to a hematology/oncology practice. Similarities included specialties of referring physicians, mean ages, proportions of women, reactivity to Pneumovax, median serum IgG3 and IgG4 levels, median blood CD56+/CD16+ lymphocyte levels, positivity for HLA-A and -B types, and frequencies of selected HLA-A, -B haplotypes. Dissimilarities included greater prevalence of autoimmune conditions, lower median IgG, IgA, and IgM, and lower median CD19+, CD3+/CD4+, and CD3+/CD8+ blood lymphocytes in CVID patients. Prevalence of Sjögren's syndrome and hypothyroidism was significantly greater in CVID patients. Combined subnormal IgG1/IgG3 occurred in 59% and 29% of CVID and IgGSD patients, respectively. Isolated subnormal IgG3 occurred in 121 IgGSD patients (88% women). Logistic regression on CVID (versus IgGSD) revealed a significant positive association with autoimmune conditions and significant negative associations with IgG1, IgG3, and IgA and CD56+/CD16+ lymphocyte levels, but the odds ratio was increased for autoimmune conditions alone (6.9 (95% CI 1.3, 35.5)).


Assuntos
Imunodeficiência de Variável Comum/genética , Imunodeficiência de Variável Comum/imunologia , Deficiência de IgG/genética , Deficiência de IgG/imunologia , Adulto , Doenças Autoimunes/imunologia , Complexo CD3/imunologia , Complexo CD3/metabolismo , Antígeno CD56/imunologia , Antígeno CD56/metabolismo , Imunodeficiência de Variável Comum/sangue , Feminino , Antígenos HLA-A/genética , Antígenos HLA-A/imunologia , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Haplótipos/genética , Haplótipos/imunologia , Humanos , Deficiência de IgG/sangue , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Modelos Logísticos , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Vacinas Pneumocócicas/imunologia , Receptores de IgG/imunologia , Receptores de IgG/metabolismo , Encaminhamento e Consulta , Streptococcus pneumoniae/imunologia
15.
BMC Immunol ; 15: 43, 2014 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-25339459

RESUMO

BACKGROUND: Our informal observations suggested that some patients with acute sensorineural hearing loss (ASNHL) have subnormal serum immunoglobulin (Ig) levels. We evaluated 28 consecutive adults (18 men, 10 women) at ASNHL diagnosis using: antibodies to 68 kD protein, 30 kD protein, and type II collagen; and serum total IgG, IgG subclasses, total IgA, and IgM. Reference ranges for Ig levels were mean ± 2 SD. We compared prevalences of subnormal IgG subclasses to those in 275 healthy European adults in previous reports. We also reviewed charts of consecutive adult index patients with primary Ig deficiency (35 common variable immunodeficiency, 406 IgG subclass deficiency) to identify other patients with probable ASHNL. RESULTS: Mean age was 53 ± 10 (SD) y. Six patients (21.4%) had other autoimmunity manifestations. Antibodies to 68 kD protein, 30 kD protein, and type II collagen were detected in 21.4% (6/28), 21.1% (4/19) and 18.8% (3/16), respectively. Three patients (10.7%) had subnormal IgG1, six (21.4%) had subnormal IgG3, and four (14.3%) had subnormal IgG1 and IgG3. Some had subnormal IgG2, IgG4, IgA, and IgM (n = 1, 2, 3, and 1, respectively). Prevalences of subnormal IgG1 or IgG3 were greater in ASNHL patients (25.0% and 35.7%) than 275 controls (2.1% and 3.3%), respectively (p < 0.0001, each comparison). Relative risks of subnormal IgG1 and IgG3 in ASNHL were 11.5 [95% CI: 4.1, 31.7] and 10.9 [4.8, 25.6], respectively. Hearing improved after initial therapy in 17 patients (60.7%). Multiple regressions on Ig levels revealed no significant associations with other available variables. Logistic regressions on initial therapy response revealed a positive association with men (p = 0.0392) and a negative association with IgA (p = 0.0274). Our estimated prevalence of probable ASNHL in 35 patients with common variable immunodeficiency during a follow-up interval of 8 ± 4 y was 0% [95% CI: 0, 12.3]). Prevalence of probable ASNHL in 406 patients with IgG subclass deficiency during the same interval was 0.74% [0.19, 2.33]. CONCLUSIONS: Serum levels of IgG1 or IgG3 were subnormal in 46.4% of 28 patients with ASNHL. Among adults who present with primary Ig deficiency, some may have or later develop ASNHL.


Assuntos
Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , Perda Auditiva Neurossensorial/sangue , Perda Auditiva Neurossensorial/imunologia , Imunoglobulina G/sangue , Adulto , Autoanticorpos/sangue , Doenças Autoimunes/complicações , Orelha Interna/imunologia , Feminino , Perda Auditiva Neurossensorial/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Regressão , Infecções Respiratórias/complicações , Fatores de Risco , Resultado do Tratamento
16.
J Clin Immunol ; 34 Suppl 1: S35-45, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24793544

RESUMO

IgM exists as both a monomer on the surface of B cells and a pentamer secreted by plasma cells. Both pre-immune "natural" and antigen-induced "immune" IgM antibodies are important for protective immunity and for immune regulation of autoimmune processes by recognizing pathogens and self-antigens. Effector proteins interacting with the Fc portion of IgM, such as complement and complement receptors, have thus far been proposed but fail to fully account for the IgM-mediated protection and regulation. A major reason for this deficit in our understanding of IgM function seems to be lack of data on a long elusive Fc receptor for IgM (FcµR). We have recently identified a bona fide FcµR in both humans and mice. In this article we briefly review what we have learned so far about FcµR.


Assuntos
Linfócitos B/imunologia , Imunoglobulina M/imunologia , Receptores Fc/imunologia , Animais , Autoantígenos/imunologia , Humanos , Imunomodulação , Camundongos , Receptores Fc/isolamento & purificação
17.
Am J Med Sci ; 343(1): 106-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22008780

RESUMO

Acute kidney injury (AKI) is a rare complication of carcinoid syndrome. A 61-year-old man developed carcinoid syndrome 51 months after pneumonectomy for bronchial carcinoid, and 8 episodes of AKI 101 to 118 months after pneumonectomy. Serum chromogranin A and urine 5-hydroxyindoleacetic acid levels were elevated for more than 1 year before AKI occurred. Each episode was characterized by flushing, facial edema, mild diarrhea, necrosis of hepatic metastatic nodules, mild oliguria, hyponatremia, acidosis, hypokalemia, hypomagnesemia and hyperphosphatemia. He did not have elevated urine sodium levels or osmolality, hypotension or hypertension. Plasma levels of dopamine, epinephrine and norepinephrine, measured during a single episode, were markedly elevated. Serum creatinine levels returned to normal after most episodes. Hyponatremia persisted but was more severe during AKI. Elevated plasma levels of vasoactive substances other than 5-hydroxytryptamine, perhaps dopamine or other catecholamines, could explain recurrent AKI. The natriuretic effect of elevated plasma dopamine levels could explain chronic hyponatremia.


Assuntos
Lesão Renal Aguda/etiologia , Neoplasias Brônquicas/complicações , Síndrome do Carcinoide Maligno/complicações , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva
18.
Infect Dis Rep ; 4(2): e34, 2012 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-24470948

RESUMO

We sought to determine predictors of shingles reports in adults with common variable immunodeficiency or immunoglobulin (Ig) G subclass deficiency (CVID/IgGSD). We tabulated observations at diagnosis of CVID/IgGSD in 212 white adult index patients (165 women, 47 men) who responded to a question about having had shingles. None had been vaccinated for herpes zoster. We analyzed age, sex, and shingles reports; blood levels of CD19+, CD4+, CD8+, and CD56+ mononuclear cells; serum levels of IgG subclasses, IgA, and IgM; and positivity for human leukocyte antigen (HLA)-A and -B haplotypes. Cell counts and immunoglobulin levels were normalized with loge (ln) transformation for analyses. Thirty-one patients (14.6%) reported shingles; 11 reported recurrent or disseminated shingles. Patients with shingles reports had greater mean age at diagnosis of CVID/IgGSD [54±13 (standard deviation) years vs. 47±12 years; P=0.0130] and a greater prevalence of HLA-A*01, B*08 positivity (35.5% vs. 17.7%; P=0.0227). In a 13-factor logistic regression model, there was a positive association of age with shingles reports [P=0.0151; odds ratio (1.05, 95% confidence interval 1.01, 1.08)]. HLA-A*01, B*08 positivity was also positively associated with shingles reports [P=0.0480; odds ratio 2.61 (1.00, 6.81)]. During a mean followup interval of 7.5 years after CVID/IgGSD diagnosis, the prevalence of recurrent shingles was almost five-fold greater in patients with previous shingles reports. In conclusion, in white adults at CVID/IgGSD diagnosis, age at diagnosis and positivity for HLA-A*01, B*08 have significant positive associations with reports of previous shingles.

19.
Blood ; 118(18): 4902-9, 2011 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-21908424

RESUMO

The association of an IgM-Fc receptor (FcµR) with chronic lymphocytic leukemia (CLL) was suggested more than 30 years ago, but its authenticity has never been formally addressed. We examined the expression of the recently identified FcµR by B and T cells in CLL patients using receptor-specific monoclonal antibodies. CLL B cells (CD5(+)/CD19(+)) expressed much higher levels of FcµR on their cell surface than B cells from healthy donors. Such enhanced expression was more evident in immunoglobulin heavy chain variable region (IGHV)-mutated, CD38(-) or early Rai-stage CLL than in IGHV-unmutated, CD38(+), or advanced Rai-stage CLL. Intriguingly, surface FcµR levels also were significantly elevated in the non-CLL B cells (CD5(-)/CD19(+)) and T cells (CD5(+)/CD19(-)), especially in IGHV-mutated CLL. CLL patients also had high serum titers of FcµR compared with healthy donors, and serum FcµR levels correlated significantly with circulating lymphocyte numbers but not with the IGHV mutation status or Rai stage. The serum FcµR was resolved as an ∼ 40-kDa protein, distinct from the cell surface FcµR of ∼ 60 kDa, and it was produced by both CLL B and non-CLL B cells. Mass spectrometric analysis revealed that the serum FcµR is a soluble form of the receptor encoded by an alternatively spliced FcµR transcript. These findings indicate enhanced levels of both membrane-bound and soluble forms of FcµR in CLL patients.


Assuntos
Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/metabolismo , Proteínas de Membrana/metabolismo , Receptores Fc/sangue , Receptores Fc/metabolismo , Sequência de Aminoácidos , Antígenos de Superfície/sangue , Antígenos de Superfície/genética , Antígenos de Superfície/metabolismo , Células Cultivadas , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Proteínas de Membrana/química , Proteínas de Membrana/genética , Dados de Sequência Molecular , Isoformas de Proteínas/sangue , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores Fc/química , Receptores Fc/genética , Solubilidade , Regulação para Cima
20.
BMC Blood Disord ; 10: 9, 2010 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-21176208

RESUMO

BACKGROUND: There are many descriptions of the association of pica with iron deficiency in adults, but there are few reports in which observations available at diagnosis of iron deficiency were analyzed using multivariable techniques to identify significant predictors of pica. We sought to identify clinical and laboratory correlates of pica in adults with iron deficiency or depletion using univariable and stepwise forward logistic regression analyses. METHODS: We reviewed charts of 262 non-pregnant adult outpatients (ages ≥18 y) who required treatment with intravenous iron dextran. We tabulated their sex, age, race/ethnicity, body mass index, symptoms and causes of iron deficiency or depletion, serum iron and complete blood count measures, and other conditions at diagnosis before intravenous iron dextran was administered. We excluded patients with serum creatinine >133 µmol/L or disorders that could affect erythrocyte or iron measures. Iron deficiency was defined as both SF <45 pmol/L and TS <10%. Iron depletion was defined as serum ferritin (SF) <112 pmol/L. We performed univariable comparisons and stepwise forward logistic regression analyses to identify significant correlates of pica. RESULTS: There were 230 women (184 white, 46 black; ages 19-91 y) and 32 men (31 white, 1 black; ages 24-81 y). 118 patients (45.0%) reported pica; of these, 87.3% reported ice pica (pagophagia). In univariable analyses, patients with pica had lower mean age, black race/ethnicity, and higher prevalences of cardiopulmonary and epithelial manifestations. The prevalence of iron deficiency, with or without anemia, did not differ significantly between patients with and without pica reports. Mean hemoglobin and mean corpuscular volume (MCV) were lower and mean red blood cell distribution width (RDW) and platelet count were higher in patients with pica. Thrombocytosis occurred only in women and was more prevalent in those with pica (20.4% vs. 8.3%; p = 0.0050). Mean total iron-binding capacity was higher and mean serum ferritin was lower in patients with pica. Nineteen patients developed a second episode of iron deficiency or depletion; concordance of recurrent pica (or absence of pica) was 95%. Predictors of pica in logistic regression analyses were age and MCV (negative associations; p = 0.0250 and 0.0018, respectively) and RDW and platelet count (positive associations; p = 0.0009 and 0.02215, respectively); the odds ratios of these predictors were low. CONCLUSIONS: In non-pregnant adult patients with iron deficiency or depletion, lower age is a significant predictor of pica. Patients with pica have lower MCV, higher RDW, and higher platelet counts than patients without pica.

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