HLA-G genotype and HLA-G expression in systemic lupus erythematosus: HLA-G as a putative susceptibility gene in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease mainly mediated by the deposit of immune complexes and defects in T lymphocytes and antigen-presenting cells along with a high production of T-helper 2 cytokines. A tolerance-inducible function of nonclassical class Ib human leukocyte antigen (HLA)-G molecule in innate and adaptive cellular responses has been reported, suggesting a role in inflammatory diseases. A 14 bp sequence insertion/deletion polymorphism (rs16375) in the 3'-untranslated region of the HLA-G gene has been associated to the stability of HLA-G messenger RNA. The insertion of the 14 bp sequence seems to be associated with lower levels of soluble HLA-G (sHLA-G). The aim of this study was to evaluate the possible association of the presence of the 14 bp sequence (+14 bp) with SLE. We have HLA-G genotyped 200 SLE patients and 451 healthy control subjects (HS; Italian) and analyzed the plasma levels of sHLA-G and interleukin-10 (IL-10) in a subset of SLE patients and healthy subjects (Italian and Danish). A significant increase of the +14 bp HLA-G allele was detected in the Italian SLE patients compared with HS [P = 0.003, OR 1.44 (95% CI 1.13-1.82)]. A significant increased frequency of HLA-G +14/+14 bp and a decreased frequency of HLA-G -14/-14 bp were observed in SLE patients. There median concentration of sHLA-G was significantly lower in the plasma of SLE patients compared with that in the plasma of healthy controls (P < 0.0001). Furthermore, the results confirmed higher concentrations of IL-10-positive plasma in SLE patients. These results support a potential role for HLA-G in the susceptibility of SLE.

HLA antigens and multiple sclerosis in the Province of Ferrara, northern-Italy: a community-based study.

The association between Multiple Sclerosis (MS) and DR2 HLA antigen is well known in Caucasoids. In the past few years a significant correlation has been found between DQwl and MS in North-East Scotland and in several other countries. In previous HLA studies in Italian MS patients, a lack of any association or an increased frequency of DR2 have been observed; however, the results of most Italian surveys derive from heterogeneous sample of affected individuals. This study was carried out in a homogeneous population of patients living in and originating from the province of Ferrara, Northern-Italy. Among the prevalence cases, 116, indigenous, unrelated patients, were typed for HLA-A-B, -DR and DQ antigens. The comparisons with 185 healthy individuals, originating from the same area, revealed an increased prevalence of DR2 antigen in Ferrara MS patients. This antigen does not appear to be related to the clinical variables of the disease.

A monoclonal antibody (GF 22.1) detecting different patterns of HLA class I cross-reactivities at different dilutions.

A murine cytotoxic monoclonal antibody (GF 22.1) was produced by Balb/c immunization with GRA human lymphoblastoid cells. HLA-A, B and C blanketing and SDS-PAGE analysis of the immunoprecipitate demonstrated MHC class I structures as the targets. Cytotoxic assays were performed with peripheral blood lymphocytes from 84 unrelated donors and from members of 15 families at different antibody dilutions. Statistical analysis was performed by Fisher test on each dilution separately and by Mann-Whitney U test on the dilutions taken all together. The data suggest the detection of a cross-reacting group (B15, A32, B17, B40/w41 and B21) with high affinity and the inclusion of other antigens (B12, B35, A2, B13, A11 and A24) with a lower affinity.