ABSTRACT
Immunoglobulin G antibodies against deamidated gliadin peptides are now known to have diagnostic accuracy comparable to tissue transglutaminase and endomysium autoantibodies in patients with coeliac disease. However, little is known about their predictive value in infants with a suspected gluten enteropathy. We tested whether deamidated gliadin immunoglobulin G antibodies are more reliable than traditional tests for coeliac disease screening in infancy. Sixty-five children under 2 years of age (42 with malabsorption, 23 controls) were tested for deamidated gliadin immunoglobulin G, tissue transglutaminase and endomysium immunoglobulin A, and gliadin immunoglobulins A and G . Thirty-seven of the 42 children with malabsorption had deamidated gliadin antibodies, associated with tissue transglutaminase and endomysial antibodies in 33, and with gliadin immunoglobulins A and G in 21 and 29, respectively. Intestinal biopsy was performed in 34 of the 37 children positive for deamidated gliadin antibodies. Thirty-two/34 showed villous atrophy consistent with coeliac disease, while the remaining two had a Marsh 1 and a normal mucosa, respectively. Only gliadin immunoglobulins A (4.3%) and G (39.1%) were found in controls. The sensitivity of deamidated gliadin, tissue transglutaminase and endomysial antibodies for coeliac disease was significantly higher than that of gliadin immunoglobulins G and A. High titre deamidated gliadin antibodies correlated with severe intestinal damage. Deamidated gliadin antibodies showed a higher diagnostic accuracy for coeliac disease than gliadin antibodies in infancy. High titre deamidated gliadin antibodies predict a severe gluten-dependent duodenal damage.
Subject(s)
Antibodies/immunology , Celiac Disease/diagnosis , Celiac Disease/immunology , Gliadin/immunology , Biopsy , Child, Preschool , Female , Glutens/immunology , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Infant , Intestinal Mucosa/immunology , Male , Transglutaminases/immunologyABSTRACT
Antimitochondrial antibodies are the serological hallmark of primary biliary cirrhosis (PBC). Besides antimitochondrial antibodies, the autoantibody profile of PBC includes antinuclear antibodies (ANA) which are detectable by indirect immunofluorescence in up to 50% of PBC patients. Two immunofluorescence patterns are considered 'PBC-specific': the multiple nuclear dots and rim-like/membranous patterns. The target antigens of the multiple nuclear dots pattern have been identified as Sp100 and promyelocytic leukemia protein, whereas the rim-like/membranous pattern is given by autoantibodies recognizing multiple proteins such as gp210, nucleoporin p62 and the lamin B receptor. Other ANA, especially those already known in the rheumatological setting, such as anticentromere, anti-SSA/Ro and anti-dsDNA antibodies, can be frequently found in PBC, often coexisting in the same patient. In this article, we will report on recent progress in the antigenic characterization of ANA in PBC, their detection with both traditional assays and Western blot/ELISA with molecularly defined nuclear antigens, and we will discuss their clinical significance.
Subject(s)
Antibodies, Antinuclear/immunology , Liver Cirrhosis, Biliary , Antigens, Nuclear/immunology , Autoantigens/immunology , Biomarkers/metabolism , Blotting, Western/methods , Enzyme-Linked Immunosorbent Assay/methods , Epitope Mapping , Fluorescent Antibody Technique, Indirect/methods , Humans , Liver Cirrhosis, Biliary/diagnosis , Liver Cirrhosis, Biliary/immunology , Membrane Glycoproteins/immunology , Nuclear Pore Complex Proteins/immunology , Nuclear Proteins/immunology , Prognosis , Promyelocytic Leukemia Protein , Receptors, Cytoplasmic and Nuclear/immunology , Transcription Factors/immunology , Tumor Suppressor Proteins/immunology , Lamin B ReceptorABSTRACT
GOALS: To characterize the serological pattern of gluten sensitivity (GS) and to compare it with that found in celiac disease. BACKGROUND: GS has recently been identified as a new clinical entity included in the spectrum of gluten-related disorders, but it is still lacking of diagnostic markers. STUDY: Sera from 78 patients with GS and 80 patients with celiac disease were retrospectively assessed for immunoglobulin (Ig)G/IgA antigliadin antibodies (AGA), IgG deamidated gliadin peptide antibodies (DGP-AGA), IgA tissue transglutaminase antibodies (tTGA), and IgA endomysial antibodies (EmA). RESULTS: IgG AGA were positive in 56.4% of GS patients and in 81.2% of celiac patients, with high antibody titers in both groups. IgA AGA were detected in 7.7% of GS patients and in 75% of celiac patients, showing lower enzyme-linked immunosorbent assay activities in GS than those found in celiac disease. Only 1 of the 78 patients with GS was positive for IgG DGP-AGA (detected in 88.7% of patients with celiac disease). IgA tTGA and IgA EmA were negative in all GS patients, whereas their positivity in celiac patients was 98.7% and 95%, respectively. Patients with GS displayed a variegated clinical picture with intestinal and extraintestinal symptoms (abdominal pain, bloating, diarrhea, constipation, foggy mind, tiredness, eczema/skin rash, headache, joint/muscle pain, numbness of legs/arms, depression, and anemia) together with normal or mildly abnormal small intestinal mucosa. CONCLUSIONS: The serological pattern of GS is characterized by IgG AGA positivity in more than half of cases associated to IgA AGA in a few patients, but without EmA, tTGA, and DGP-AGA, which are the specific markers of celiac disease.
Subject(s)
Food Hypersensitivity/diagnosis , Food Hypersensitivity/immunology , Glutens/immunology , Immunoglobulin G/blood , Adolescent , Adult , Antibodies/blood , Biomarkers/blood , Celiac Disease/diagnosis , Celiac Disease/immunology , Female , Gliadin/immunology , Humans , Immunoglobulin A/blood , Intestinal Mucosa/immunology , Male , Middle Aged , Transglutaminases/immunology , Young AdultABSTRACT
OBJECTIVES: During the last decade patients with concomitant clinical, biochemical, immunoserological, and histological features of both autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) were sporadically described, but definite diagnostic criteria and specific serological markers to support the diagnosis of AIH/PBC overlap syndrome (AIH/PBC OS) are still lacking. METHODS: Clinical, biochemical, and histological features, autoantibody profile, and treatment response of 15 patients with coexistent hepatitic and cholestatic liver damage, all fulfilling strict diagnostic criteria for both AIH and PBC, were compared with those of 120 patients with pure PBC and 120 patients with pure AIH. RESULTS: At diagnosis, the AIH/PBC OS patients' median age was 51 years, similar to that of the PBC patients (52 years, P=NS), but significantly higher than that of the AIH patients (40 years, P=0.04). Anti-dsDNA antibodies were detected in 60% of AIH/PBC OS patients, but only in 4% of PBC patients and 26% of AIH patients (P<0.0001 and 0.01, respectively). Double positivity for antimitochondrial antibodies (AMA) and anti-dsDNA was present in 47% of those with AIH/PBC OS, but only in 2% of the pathological controls (P<0.0001; specificity: 98; 95% confidence interval (CI): 97-99.2; positive likelihood ratio: 28; 95% CI: 9.8-79.4). Combined therapy (ursodeoxycholic acid (UDCA) plus steroids) achieved biochemical response in 77% of AIH/PBC OS patients. CONCLUSIONS: Concomitant AMA/anti-dsDNA seropositivity can be considered the serological profile of AIH/PBC OS. The combination of UDCA and steroids is effective in achieving persistent biochemical amelioration in most AIH/PBC OS patients.
Subject(s)
Antibodies, Antinuclear/immunology , Hepatitis, Autoimmune/immunology , Liver Cirrhosis, Biliary/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy , Child , Child, Preschool , Female , Fluorescent Antibody Technique, Indirect , Hepatitis, Autoimmune/complications , Hepatitis, Autoimmune/diagnosis , Humans , Liver/pathology , Liver Cirrhosis, Biliary/complications , Liver Cirrhosis, Biliary/diagnosis , Male , Middle Aged , Mitochondria, Liver/immunology , Prognosis , Radiography, Abdominal , Retrospective Studies , Syndrome , Young AdultABSTRACT
OBJECTIVE: To evaluate HIV-1 DNA load in PBLs and monocytes from both long-term HAART-treated and antiretroviral naïve HIV-1 infected patients. METHODS: Cross-sectional quantitative analysis of HIV-1 DNA load was performed in PBLs and monocytes, purified from 34 long-term HAART-treated and 34 naïve HIV-1 infected patients, and compared to RNA viral load and CD4+ cell count. RESULTS: HAART-treated patients showed significantly lower levels of viral DNA both in PBLs and monocytes in comparison with naïve individuals. Variable levels of HIV-1 DNA amount in monocytes were detected in all naïve patients but only in 12 of 34 HAART-treated individuals. PBLs HIV-1 DNA load was inversely correlated to CD4+ cell count in naïve and HAART-treated patients whereas no association was detected in monocytes. CONCLUSIONS: Long-term HAART decreased HIV-1 DNA load in PBLs and monocytes demonstrating a valuable inhibitor effect, especially in short-lived reservoirs. In addition, the positive correlation of DNA burden between PBLs and monocytes may suggest a dynamic relation between these reservoirs in the course of disease. HIV-1 DNA load quantitative analysis in PBLs and monocytes may be considered an important approach to study the HIV-1 reservoir and the effectiveness of HAART therapy in HIV-1 seropositive patients.
Subject(s)
Antiretroviral Therapy, Highly Active , DNA, Viral/analysis , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/genetics , Lymphocytes/virology , Monocytes/virology , Viral Load , Adult , Aged , CD4 Lymphocyte Count , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , RNA, Viral/bloodABSTRACT
Osteopenia and osteoporosis are common in HIV-1-infected individuals and represent a challenge in clinical and therapeutic management. This report investigated osteopenia/osteoporosis in a group of 31 antiretroviral naive HIV-1-positive men and the role of specific molecules belonging to TNF and the TNF-receptor family in HIV-1-related bone mass loss. Osteoprotegerin (OPG), the receptor activator of NF-kappab-ligand (RANKL), and the TNF-related apoptosis-inducing ligand (TRAIL) were significantly increased in the plasma of antiretroviral naive HIV-1-positive patients compared to a control group of healthy blood donors. In addition, TRAIL and RANKL plasma concentrations were positively correlated to HIV-1-RNA viral load. Measurement of bone mineral density in 20 out of 31 HIV-1-positive subjects disclosed osteopenia/osteoporosis in 40% of these patients. The antiretroviral naive HIV-1-positive subjects with low bone mineral density had a decreased plasma OPG/RANKL ratio and a plasma RANKL concentration >500 pg/ml. Together, these data indicate that plasma concentrations of specific factors involved in bone homeostasis were increased during HIV-1 infection and that RANKL and OPG/RANKL ratio deregulation may be involved in osteopenia/osteoporosis occurring in antiretroviral naive HIV-1 individuals.
Subject(s)
HIV Seropositivity/blood , HIV-1 , Osteoprotegerin/blood , RANK Ligand/blood , TNF-Related Apoptosis-Inducing Ligand/blood , Absorptiometry, Photon , Adult , Bone Density , Bone Diseases, Metabolic/diagnosis , Bone Diseases, Metabolic/etiology , Bone and Bones/metabolism , HIV Seropositivity/complications , HIV-1/genetics , HIV-1/isolation & purification , Humans , Male , Middle Aged , Osteoporosis/diagnosis , Osteoporosis/etiology , Viral LoadABSTRACT
To investigate the mechanisms involved in the human immunodeficiency virus type 1 (HIV-1)-related thrombocytopenia (TP), human umbilical cord blood (UCB) CD34(+) hematopoietic progenitor cells (HPCs) were challenged with HIV-1(IIIb) and then differentiated by thrombopoietin (TPO) towards megakaryocytic lineage. This study showed that HIV-1, heat-inactivated HIV-1, and HIV-1 recombinant gp120 (rgp120) activated apoptotic process of megakaryocyte (MK) progenitors/precursors and decreased higher ploidy MK cell fraction. All these inhibitory effects on MK survival/maturation and platelets formation were elicited by the interaction between gp120 and CD4 receptor on the cell membrane in the absence of HIV-1 productive infection. In fact, in our experimental conditions, HPCs were resistant to HIV-1 infection and no detectable productive infection was observed. We also evaluated whether the expression of specific cytokines, such as TGF-beta1 and APRIL, involved in the regulation of HPCs and MKs proliferation, was modulated by HIV-1. The specific protein and mRNA detection analysis, during TPO-induced differentiation, demonstrated that HIV-1 upregulates TGF-beta1 and downregulates APRIL expression through the CD4 engagement by gp120. Altogether, these data suggest that survival/differentiation of HPCs committed to MK lineage is negatively affected by HIV-1 gp120/CD4 interaction. This long-term inhibitory effect is also correlated to specific cytokines regulation and it may represent an additional mechanism to explain the TP occurring in HIV-1 patients.