Association between HLA class II antigens and hepatitis C virus infection

The aim was to confirm the influence of HLA Class II antigens on the progression of HCV infection and to assess the relationship between these antigens and histological damage, HCV viral load and HCV genotype. 143 patients were enrolled and divided into three groups. Group A included 34 anti-HCV positive, HCV-RNA negative patients with ALT persistently normal; group B included 39 patients with HCV-RNA positive and abnormal ALT level; group C included 70 normal subjects. Serological HCL typing was performed with lymphocytotoxicity test by Terasaky and McClelland, using lymphobeads HLC class II. The frequency of HLA DR11 (5) was significantly higher in the control group (52.9%) and in group A (64.7%), than in group B (28.2%). Allele HLA DR6 was demonstrated in a similar proportion (26%) among control group and group B, while HLA DR14 (6) was less frequent among controls (18% vs 1.4%). In group A the frequency of HLA DR14 (6) was 3% compared to group B, HLA DR17 (3) was prevalent (15.4%) in group B. Liver damage was associated with the detection of HLA DR14 (6) and HLD DR17 (3) antigens. Significantly lower levels of HCV-RNA were measured in subjects with HLA DR11 (5) than in these with either DR6 or DR17 (3). HLA class II antigens appear crucial for resolution or progression of HCV hepatitis. The punctual identification of these genetic factors may, therefore, prove to be useful in predicting disease evolution, in guiding the appropriate therapy for patients with poor prognosis, and in encouraging the development of now therapeutic strategies.     

Moesin and Stress-Induced Phosphoprotein-1 Are Possible Sero-Diagnostic Markers of Psoriasis

To identify diagnostic markers for psoriasis vulgaris and psoriatic arthritis, autoantibodies in sera from psoriasis vulgaris and psoriatic arthritis patients were screened by two-dimensional immunoblotting (2D-IB). Based on 2D-IB and MADLI TOF/TOF-MS analyses, eleven proteins each in psoriasis vulgaris and psoriatic arthritis were identified as autoantigens. Furthermore, serum levels of moesin, keratin 17 (K17), annexin A1 (ANXA1), and stress-induced phophoprotein-1 (STIP1), which were detected as autoantigens, were studied by dot blot analysis with psoriasis patients and healthy controls. The levels of moesin and STIP1 were significantly higher in sera from patients with psoriasis vulgaris than in the controls (moesin: P<0.05, STIP1: P<0.005). The area under the curve (AUC) for moesin and STIP1 between patients with psoraisis vulgaris and controls was 0.747 and 0.792, respectively. STIP1 and K17 levels were significantly higher in sera from patients with psoriatic arthritis than in those with psoriasis vulgaris (P<0.05 each). The AUC for STIP1 and K17 between patients with psoriatic arthritis and psoriasis vulgaris was 0.69 and 0.72, respectively. The STIP1 or moesin, CK17 serum level was not correlated with disease activity of psoriasis patients. These data suggest that STIP1 and moesin may be novel and differential sero-diagnostic markers for psoriasis vulgaris and psoriatic arthritis.     

HLA antigens and acetylcholine receptor antibodies in penicillamine induced myasthenia gravis.

Antibodies to the acetylcholine receptor and HLA antigens have been studied in patients with myasthenia gravis occurring in association with penicillamine treatment. The properties of the antiacetylcholine receptor in these patients differed from those in patients with idiopathic myasthenia gravis in terms of specificity and affinity. These patients had an increased prevalence of HLA Bw35 and DR1 compared to controls and a decreased frequency of B8 and DR3 compared to patients with idiopathic myasthenia gravis. Likewise, they had a decreased frequency of DR4 compared to patients with rheumatoid arthritis. These data provide supportive evidence for a role for penicillamine in the induction of myasthenia gravis in genetically predisposed individuals.     

Influence of HLA genotype on birth weight of patients with Turner syndrome

Summary Growth failure starting before birth is a common characteristic in Turner syndrome, and its pathogenesis is still not completely explained. Experiments performed in mice and rats to test whether a genetic disparity between mothers and offspring and maternal immunological status have any influence on litter size have demonstrated that allogenic litters are significantly larger in size than genetically compatible ones. Studies in humans have given contrasting results, but some authors have found that heterozygosity at enzyme loci and in blood groups is positively correlated with intrauterine growth. HLA class I and II polymorphisms were defined in 53 patients with Turner syndrome and in their parents, and lymphocytotoxic antibody detection was performed in 36 mothers. These data were related to the patients' birth weight. The frequency of the HLA-B16 allele in patients with a birth weight > 10th centile was significantly higher in comparison with those < 10th centile. HLA antigen sharing was present in 43 couples (81.1%). Mean birth weight was 2934 ± 472 g in patients without HLA antigen parental sharing and 2721 ± 529 g in those whose parents shared HLA antigens. The mean birth weight of the 10 patients whose parents do not share HLA antigens was significantly higher than that of the patients with parental HLA–B+DR sharing (P < 0.05) and not significantly higher than in those patients with parental HLA sharing at other HLA loci. Patients whose parents shared B+DR antigens also had significantly smaller birth weights than those with B and A+B+DR sharing (P < 0.025 and P < 0.025). No significant difference in mean birth weight was found in relation to other parameters, such as mother-child histocompatibility, HLA homozygosity and lymphocytotoxic production in the mothers.     

Complement phenotypes in patients with psoriasis

Phenotype frequencies for the complement proteins C4A, C4B, Bf (factor B) and C3 were performed for 49 Caucasian patients with psoriasis. The C4*A6 allele was present in 26.6% of the patients as compared to 5.4% of healthy regional Caucasian controls, p less than 0.001, relative risk = 6.28. The C4*A6 allele is known to be in linkage disequilibrium with the HLA B17 allele and to produce a non-functional gene product when it occurs with the B17 allele. HLA B17 is known to be associated with psoriasis in many Caucasian populations. Additional findings in the present study were a significant reduction in the C4B*2 allele frequency, a non-significant increase in the Bf*F allele frequency and no difference for Bf or C3 phenotype frequencies in the patients with psoriasis as compared to the controls.     

Genetic determination of rheumatoid arthritis. Distribution of certain Mendelian markers in the light of correspondence of the disease heritability to the model of single autosomal two-allele locus with incomplete penetrance

The study on the nature of distribution of certain mendelian markers aimed at specifying their role in determination of rheumatoid arthritis disease was carried out, based on the material from the Family Data Bank of the Department of Epidemiology and Genetics of the rheumatic diseases in this institute comprising data on 200 families of patients with definite rheumatoid arthritis (RA). Antigens of HLA-system (the loci A, B, DR), ABO blood groups, Rh, MN and P, phenotypes of acid erythrocyte phosphatase and the types of haptoglobin were studied. Based on the data from this and the previous studies, it is established that the steadiest deviations of the RA patients groups from the general population concerned the frequency of HLA A11, B12, B27 and DR4, blood group P and phenotypes of the acid erythrocyte phosphatase. When using additional controls--a group of healthy mothers of women-probands from the families with the type of marriage "healthy x healthy", and analysing some pair combinations of the HLA system antigens, it was demonstrated that the most clearly their role in formation of the disease display the antigens DR4, and in their absence--DR3, and B12, whereas accumulation of A11 and B27 depended on the presence of other antigens of HLA loci--A and B. Taken together, these data may imply that genetic markers under study serve, when in certain combinations, as "modifiers" of the major gene, or, in a general case, of major genes of multifactorial disease affecting its appearance and clinical manifestations.     

Susceptibility alleles and haplotypes of human leukocyte antigen DRB1, DQA1, and DQB1 in autoimmune polyglandular syndrome type III in Japanese population

BACKGROUND: It has been reported that HLA class II haplotypes DRB1*0405-DQA1*0303-DQB1*0401 and DRB1*0901-DQA1*0302-DQB1*0303 are major susceptibility haplotypes for type 1 diabetes mellitus (DM) in Japanese population. However, little has been reported on the susceptibility HLA class II haplotypes in Japanese patients with autoimmune polyglandular syndrome type II and type III (APS III). PATIENTS AND METHODS: HLA class II haplotypes of DRB1-DQA1-DQB1 in 31 patients with APS III, 14 patients with Hashimoto's thyroiditis alone, and 15 patients with Graves' disease alone were examined in Japanese population. APS III patients were divided into three groups (A, B, and C) depending on the combination of autoimmune endocrine diseases. RESULTS: In 13 APS III patients with both Hashimoto's thyroiditis and type 1 DM (group A), the haplotype frequencies of the HLA DRB1*0802-DQA1*0401-DQB1*0402 and DRB1*0901-DQA1*0302-DQB1*0303 were significantly higher than in the controls. In patients with Hashimoto's thyroiditis alone, the haplotype frequency of DRB1*0901-DQA1*0302-DQB1*0303 was significantly higher than in controls, whereas the frequency of DRB1*0802-DQA1*0401-DQB1*0402 did not differ significantly from those in the controls. In 11 APS III patients with both Graves' disease and type 1 DM (group B), the haplotype frequencies of HLA DRB1*0405-DQA1*0303-DQB1*0401 and DRB1*0802-DQA1*0301-DQB1*0302 were significantly higher than in controls. In patients with Graves' disease alone, the haplotype frequency of DRB1*0803-DQA1*0103-DQB1*0601 were significantly higher than those in controls, suggesting that the susceptibility haplotypes for group B APS III differed from those for Graves' disease alone. In 7 APS III patients with both autoimmune thyroid diseases and pituitary disorders (group C), the haplotype frequency of HLA DRB1*0405-DQA1*0303-DQB1*0401 was significantly higher than in controls. CONCLUSIONS: Susceptible HLA class II haplotypes of DRB1-DQA1-DQB1 for APS III differ between the Japanese and Caucasian populations. More interestingly, the susceptible HLA class II haplotypes differ among the three types of Japanese APS III and are not merely a combination of susceptibility haplotypes of each endocrine disease.     

HLA antigens in patients with and without a family history of schizophrenia

Frequencies of HLA antigens (A, B, C and DR) were studied in patients with (n = 49) and without (n = 67) a family history of schizophrenia and in controls. Among the patients with a family history of schizophrenia significant increases were found in the A3 and B5 antigens while significant decreases were observed for the A1, A11 and B8 antigens. In a material of schizophrenic siblings the sharing of HLA haplotypes was consistent with normal segregation.     

HLA as a marker of the hemochromatosis gene in Sweden

Summary The frequency of HLA-A3 and HLA-B14 antigens was found to be significantly (P=<0.0001) higher in a series of 50 unrelated and unselected Swedish patients with idiopathic hemochromatosis (IH) than in controls, being 66% and 32% for A3 and 22% and 2% for B14. The haplotype A3B14 was associated with the highest risk in this material (relative risk 23.4). One family with this haplotype was traced back to the end of the seventeenth century. The pattern of HLA antigens associated with IH in Sweden shows remarkable similarity to those reported from England and Brittany.     

Susceptibility of major groups of Tamil Nadu to diseases: 1. Psoriasis vulgaris

Eighty-three patients with psoriasis vulgaris, living in Madurai, Tamil Nadu, India, were studied for HLA-A, HLA-B, HLA-C, HLA-DR and HLA-DQ antigen frequencies and compared with seventy-seven controls studied using the same batch of reagents. A highly significant increase of frequency of HLA-Bw57, a split of HLA-B 17, was found in the patients; Bw58, another split of B17, was absent. Relative risk was high for A1, B17, Bw57 and DR7 individuals; it was highest for Bw57. Frequencies of the haplotypesAl-Bw57 andDR7-DQw3 were also significantly higher in patients. Analysis of the HLA data based on ethnic differences identified as major groups revealed high relative risk for B17, Bw57 and DR7 only in major group III, a Western brachycephal Armenoid group, but not in major group II, a Mediterranean one thought to be an earlier settler of this region. Analysis of the data based on age and sex subgroups yielded interesting information. The age at onset of the disease in the total patient sample showed a bimodal distribution. The two sexes differed in their age-at-onset distributions: females showed a preponderance of early onset of the disease (< 30 years of age, 68%), while the majority of males had late onset (>30 years of age, 71%). HLA data for the early-onset patients indicate very high relative risk for B17, Bw57 and DR7. This suggests that psoriasis may be influenced by sex, and that the early-onset and late-onset forms of the disease may be of different aetiopathogenesis. These observations stress the importance of considering the ethnic origin or composition of samples, and age, sex and other parameters in HLA and disease association studies.     

Effect of Vitamin D on Peripheral Blood Mononuclear Cells from Patients with Psoriasis Vulgaris and Psoriatic Arthritis

BackgroundPsoriasis, a chronic skin disease with or without joint inflammation, has increased circulating proinflammatory cytokine levels. Vitamin D is involved in calcium homeostasis, bone formation, osteoclastogenesis and osteoclast activity, as well as regulation of immune response. We aimed to study osteoclast differentiation and cytokine secretion of peripheral blood mononuclear cells (PBMCs) from patients with psoriasis vulgaris and psoriatic arthritis, in response to 1,25(OH)₂D₃.MethodsSerum levels of bone turnover markers were measured by ELISA in patients with psoriasis vulgaris and psoriatic arthritis, and healthy controls. PBMCs were isolated and cultured with or without RANKL/M-CSF and 1,25(OH)₂D₃. Osteoclast differentiation and cytokine secretion were assessed.ResultsPsoriatic arthritis patients had lower osteocalcin, as well as higher C-telopeptide of type I collagen and cathepsin K serum levels compared with psoriasis vulgaris patients and controls. RANKL/M-CSF-stimulated PBMCs from psoriatic arthritis patients produced higher proinflammatory cytokine levels and had a differential secretion profile in response to 1,25(OH)₂D₃, compared with psoriasis vulgaris and control PBMCs.ConclusionsOur data confirmed altered bone turnover in psoriatic arthritis patients, and demonstrated increased osteoclastogenic potential and proinflammatory cytokine secretion capacity of these PBMCs compared with psoriasis vulgaris and controls. 1,25(OH)₂D₃ abrogated these effects.     

Association of HLA DR1 with high D-penicillamine binding to monocytes in females

Binding of D-Penicillamine (D-Pen) to human monocytes was examined by flow cytometry with fluorescent D-Pen conjugate. Cells from HLA DR1-positive healthy females bound significantly more D-Pen than cells from DR1-negative healthy females (P = 0.015), and DR1 was associated with the highest binding among HLA DR antigens. In contrast, DR4 was associated with the lowest binding in healthy females. A difference in D-Pen binding between healthy females who were DR1-positive, DR4-negative and those who were DR1-negative, DR4-positive was statistically significant (P = 0.026). Neither healthy females nor healthy males showed significant associations of D-Pen binding with HLA A, B, or C antigens, nor did healthy males show an association between strength of D-Pen binding and any DR antigens.     

Heterogeneity of non-insulin-dependent diabetes mellitus in HLA types and clinical features: comparison with insulin-dependent diabetes mellitus

We determined HLA types in 110 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) and studied the relationship between the HLA phenotypes and clinical features. Sixty-nine patients with insulin-dependent diabetes mellitus (IDDM) and 100 healthy blood donors served as controls. Concerning HLA DR and DQ loci, frequencies of DR4, DRw9 and DQw3.2 were higher, and those of DR2, DRw8, DRw11, DRw12 and DQw1 were lower in patients with IDDM compared than in healthy controls. There were no differences between NIDDM and normal controls in the frequency of a particular HLA DR antigen except for a decreased frequency in DRw11 in the former. The frequency of DQw3.2 antigen in NIDDM was intermediate between IDDM and normal controls. There were some differences between DQw3.2-positive and -negative NIDDM patients in clinical features. Those who showed low C-peptide responses during oral glucose tolerance test were more frequently found among DQw3.2-positive NIDDM patients. These results suggest that Type 1 diabetes mellitus may have a mild clinical course and is found among the Japanese NIDDM population.     

Distribution of HLA Antigens in the Armenian Population of Nagornyi Karabakh

Characteristics of the distribution of 31 HLA antigens of classes I (A, B, and Cw) and II (DR) in Nagornyi Karabakh Armenians are reported for the first time. It has been found that the antigens most common in this population are A2, A3, A9, B5, B7, B12, Cw4, DR4, DR2, and DR3; the least common antigens are B15, B16, and B40. The results are compared with the data for Armenians living in Armenia and those for major ethnic groups. The frequencies of HLA antigens in Nagornyi Karabakh Armenians match those in Armenians living in Armenia. In the HLA-antigen distribution, Armenians are generally close to Caucasoids.     

Distribution of HLA antigens in the armenian population of Nagornyi Karabakh

Characteristics of the distribution of 31 HLA antigens of classes I (A, B, and Cw) and II (DR) in Nagornyi Karabakh Armenians are reported for the first time. It has been found that the antigens most common in this population are A2, A3, A9, B5, B7, B12, Cw4, DR4, DR2, and DR3; the least common antigens are B15, B16, and B40. The results are compared with the data for Armenians living in Armenia and those for major ethnic groups. The frequencies of HLA antigens in Nagornyi Karabakh Armenians match those in Armenians living in Armenia. In the HLA-antigen distribution, Armenians are generally close to Caucasoids.     

Genetic epidemiology: Psoriatic arthritis

The existence of psoriatic arthritis as a distinct clinical entity remains a topic of debate; some authors propose that it is simply the co-occurrence of psoriasis and inflammatory arthritis. However, a distinct entity is likely to have distinct susceptibility factors in addition to those that contribute to psoriasis and inflammatory arthritis alone. These aetiological factors may be genetic and/or environmental, and in this review, the evidence for distinct psoriatic arthritis genetic susceptibility factors is considered.     

Serum lipid profile in psoriatic patients: correlation between vascular adhesion protein 1 and lipoprotein (a)

Psoriasis is a chronic inflammatory skin disease characterized by excessive cellular replication. Apolipoproteins are genetically determined molecule whose role has been implied in cardiovascular pathology. Vascular adhesion protein?1 (VAP?1) is an adhesion molecule with an enzymatic activity that partakes in the migration process of lymphocytes into sites of inflammation. Our purpose was to evaluate the plasma lipid profiles, apolipoproteins (A1, B) and Lp (a) and VAP?1 in order to compare the lipid profile in psoriatic patients with non‐affected persons and correlation between VAP?1 and Lp (a). We determined serum concentrations of lipids, lipoproteins , apolipoproteins and VAP?1 in 90 patients with psoriasis and 90 age matched controls. Serum Lp (a), apo A1 and apo B were measured by immunoprecipitation assays, and the lipids and lipoproteins were measured by enzymatic methods.The VAP?1 were masured by ELISA method. The mean levels of total cholesterol, LDL, apo B and VAP?1 in patients with psoriasis were found to be significantly higher than those of healthy subjects (P<0.05. In psoriatic patients, elevation of VAP‐1 correlated with elevation of Lp (a) (p = 0.025). This study shows that high serum lipid level and VAP?1, is significantly more common in psoriasis. This fact may be responsible for higher prevalence of cardiovascular accident in psoriatic patients. Copyright © 2012 John Wiley & Sons, Ltd.     

HLA-B57 is significantly associated with psoriasis in Northeast Romania [corrected

The aim of the study was to identify HLA class I types associated with susceptibility to psoriasis among population of Northeast region of Romania. PATIENTS AND METHODS: 27 psoriatic patients and 89 controls were typed serologically for HLA-A and HLA-B lymphocyte expression using CDC-NIH (complement dependent-cytotoxicity--National Institute of Health) method. The Terasaki plates used for HLA class I typing were prepared in our laboratory using antisera of known specificities. RESULTS AND CONCLUSIONS: psoriatic patients in the group of study frequently express HLA-B57 phenotype. The relative risk induced by this phenotype was highly statistically significant (p = 0.0016) while HLA-B13 was not associated with a significant risk for developing psoriasis in patients under study compared with controls (p = 0.48). Also, HLA-B27 (p = 0.96) and HLA-B44 (p = 0.99), reported by others to be associated with late psoriasis, do not meet (a particular) disease susceptibility between psoriatic patients under investigation.     

HLA class I and class II polymorphism in the population of Rijeka,Croatia

The aim of the study was to examine frequencies of HLA-A, -B, -DR antigens and haplotypes in population of Rijeka and to compare them with general Croatian and European populations. The subjects were 117 unrelated healthy blood donors. The antigens with the highest frequencies were: A2 (27.2%), A9 (16.3%), B5 (14.8%), B12 (11.8%), B18 (11.8%), DR5 (21.6%) and DR6 (13.8%). Comparison of HLA antigens frequencies has shown statistically significant difference in 1 antigen with Croatian population and in 8 antigens with European population. The HLA haplotypes with high frequencies included HLA-A2, B5 (6.84%), HLA-A2, B12 (6.84%), HLA-A2, B18 (6.84%), HLA-B12, DR2 (9.78%) and HLA-B18, DR5 (6.84%). The antigen B5 showed strongest association with DR5 (6.41%; LD = 1.30) as in general Croatian and in some European populations. The results have shown great diversity of HLA haplotypes in Rijeka population which can be the result of admixture with neighborhood immigrating populations during the history.