Susceptibility to ankylosing spondylitis but not disease outcome is influenced by the level of HLA-B27 expression, which shows moderate variability over time.

OBJECTIVE: Previous reports have highlighted the relevance of HLA-B27 expression in the pathogenesis of ankylosing spondylitis (AS). The aim of the current study was to estimate the level of HLA-B27 expression on the cell surface of ex vivo monocytes and lymphocytes by a quantitative method and to correlate this with AS disease susceptibility, disease clinical indexes, and the occurrence of acute anterior uveitis (AAU). METHOD: We recruited 32 B27-positive patients with AS and 32 B27-positive healthy normal controls (NCs) for evaluation at different time points. The expression of HLA-B27 molecules was quantified by flow cytometry on ex vivo peripheral blood mononuclear cells (PBMCs). Patients were also evaluated by scores on the Bath AS disease activity (BASDAI), functional (BASFI), and metrology (BASMI) indexes. RESULTS: The expression of HLA-B27 molecules was significantly higher in patients with AS than in B27-matched controls in the case of both monocytes [219K (IQR 174K-308K) vs. 137K (IQR 96K-170K), p < 0.0001] and lymphocytes [82K (IQR 58K-118K) vs. 54K (IQR 44K-61K), p < 0.0001]; AS only vs. AS with AAU: p = 0.744 in monocytes and p = 0.701 in lymphocytes. Comparisons with metrology and functional indexes were also not significant (BASMI: r = 0.05, p = 0.77; BASFI: r = -0.09, p = 0.67). The overexpression of HLA-B27 molecules was stable after 1 week of follow-up. At 3 years follow-up, the variability was moderate and did not correlate with variations in disease activity (BASDAI: r = -0.01, p = 0.92 ns). CONCLUSIONS: The level of HLA-B27 expression in PBMCs correlates with the susceptibility to AS but not with the disease outcome, nor with the occurrence of extra-articular manifestations such as AAU.

Distribution of HLA alleles and haplotypes in the Maldivian population.

The study of human leukocyte antigen (HLA), allele and haplotype frequencies within populations provides an important source of information for anthropological investigation, organ and hematopoietic stem-cell transplantation purposes as well as disease association studies. As of today, there are no data available in the literature on the HLA structure of the Maldivian population. Altogether 106 families were studied. We used the parents of each family (212 unrelated individuals) to analyze the frequencies of HLA class I and class II allele groups and haplotypes.

Association of HLA-DRB3*0202 and serum IgG antibodies to Chlamydia pneumoniae with essential hypertension in a highly homogeneous population from Majorca (Balearic Islands, Spain).

Separate studies investigating the relationship of essential hypertension (EH) with the HLA system and with Chlamydia pneumoniae (C. pneumoniae) infection have given conflicting results. Our aim was to clarify these relationships and determine whether the HLA system and C. pneumoniae infection interact with respect to the risk for EH. An association study (110 essential hypertensives and 107 controls) was conducted in a highly homogeneous population in the Balearic Island of Majorca (Spain). Molecular typing of HLA-B and HLA-DRB and quantification of serum levels of IgG antibodies to C. pneumoniae (sIgGa-Cp) were determined. Student's t-test, chi(2)-statistics, logistic regression analysis, and general linear model ANOVA were used for statistical analysis. The results showed that EH was related with HLA-DRB3*0202 in the whole study population, and with levels of sIgGa-Cp>63.5 BU/ml in the group of individuals with sIgGa-Cp>30 BU/ml (OR (95% CI) adjusted for obesity, familial history of EH and diabetes=2.06 (1.07-3.97), P=0.03, and =4.60 (1.06-19.90), P=0.04, respectively). The association between EH and sIgGa-Cp was observed in the DRB3*0202(+) individuals, but not in the DRB3*0202(-) subgroup (OR (95% CI)=11.14 (1.92-64.54), P=0.004, and =0.98 (0.22-4.43), P=0.64, respectively (P of the Mantel-Haenszel test for homogeneity of OR=0.06)). In our population, EH was positively associated with HLA-DRB3*0202 and with high levels of sIgGa-Cp. Moreover, a significant interaction of DRB3*0202 on the effect of sIgGa-Cp was observed, as the association of EH with these antibodies depended on the presence of DRB*0202.

Identification of a new allele, HLA-DRB1*1366*.

High-resolution polymerase chain reaction sequence-specific primer typing of the human leucocyte antigen (HLA)-DRB1 gene of an Italian patient candidate for bone marrow transplantation revealed a new allelic variant of HLA-DRB1*13. The sequence was named DRB1*1366, and comparison with previously described DRB1 alleles demonstrated the two closely related sequences were HLA-DRB1*1330 and HLA-DRB1*130302.

A psoriasis vulgaris protective gene maps close to the HLA-C locus on the EH18.2-extended haplotype.

We determined the molecular haplotypes of the HLA-A, HLA-C and HLA-B loci and the MHC class I-B-related (MIB) microsatellite in 179 unrelated psoriatic patients (72 familial cases) and in 120 controls. The HLA-A*3002-Cw*0501-B*1801-MIB1 haplotype showed a strong negative association with psoriasis vulgaris (PV) and in particular with familial PV, revealing the presence of a PV-protective gene. Analysis of association and linkage disequilibrium of the single alleles and the various two-three-four-locus segments of this haplotype indicated the presence of a protective gene telomeric to the HLA-C locus. This finding was confirmed in 13 informative multiplex PV families, in which at least one parent carried the EH18.2 haplotype. In two families, an affected sibling presented HLA-A/C recombination on the EH18.2 haplotype. A study of 12 polymorphic microsatellites in all members of the informative families, 145 PV patients, 120 controls and 32 EH18.2 homozygous healthy individuals demonstrated that the protection conferred by the EH18.2 haplotype lies within a 170 kb interval between the C143 and C244 loci, most probably in a 60 kb segment between the C132 and C244 loci.