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Human leukocyte antigens (HLA) have been reported to associate with the risk of aneurysmal subarachnoid hemorrhage (SAH) and poor outcome after SAH. Our aim was to identify HLA antigens that associate with the risk of fatal SAH in the Finnish population. Medical records of 600 cadaveric organ donors were reviewed to find organ donors that succumbed to SAH (n = 232) or brain trauma (n = 151). HLA antigen frequencies in these groups were compared with HLA frequencies in a reference population of 10,000 bone marrow donors. Chi-Square test with Bonferroni correction and multiplicative logistic regression models were used and false positive result probabilities (FPRP) were calculated. Alpha-level was 0.01. HLA-A3 associated with fatal SAH (p = 0.0014, OR 1.3 and 95%CI 1.1-1.6) and HLA-DR7 inversely associated with fatal SAH (p = 0.0040, OR 0.3 and 95%CI 0.2-0.6). HLA-A3 but not HLA-DR7 showed also a positive trend in donors with brain trauma. FPRP was below 0.5 for HLA-A3, but clearly above 0.5 for HLA-DR7. HLA-A3 seems to associate with fatal SAH in the Finnish population. Further studies are needed to reveal the pathobiologic mechanisms for how HLA-A3 associates with the risk of fatal SAH in Finns.

During pregnancy, the non-classical major histocompatibility complex (MHC) class I HLA-G molecule is specifically expressed in trophoblast cells at the materno-fetal interface and may exert a local control of the immune response against viral infections. Human cytomegalovirus (HCMV) infection, which is the major cause of congenital defects, encodes multiple glycoproteins (US2, US3, US6, US10 and US11) that interrupt the MHC class I pathway of antigen presentation. The effect of some of these unique short (US) proteins on HLA-G expression has been previously studied, but little is known about the modulation of HLA-G cell surface expression during the course of HCMV infection which ensures expression of all of these US proteins. Using flow cytometry analysis, HLA-G cell surface expression was evaluated in HCMV-infected U373-HLA-G transfectant cells and compared with the modulation of the endogenous classical HLA-A2 molecules. The results indicated that HCMV infection down-modulated HLA-G cell surface expression, but later after infection and to a lesser extent than HLA-A2. Using various HLA-G/HLA-A2 chimeras, we showed that the unique structure of HLA-G cytoplasmic tail was partly involved in the resistance of HLA-G to viral down-modulation. Such limited down-modulation of HLA-G may have functional consequences in term of innate immunity against congenital HCMV infection.

No monoclonal antibodies (mAbs) are presently available to measure the total amount of beta2-microglobulin-free HLA class I heavy chain (FHC) in sera. The available ELISA-based double determinant immunoassay (DDIA), established to measure FHC, uses two mAbs (TP25.99 and HC-10) that recognize a monomorphic determinant expressed on all HLA-B/C FHC products and a determinant expressed only on some HLA-A FHC products. This restricted reactivity implies that, in addition to HLA-B/C, HLA-A FHC products are also detected in individuals bearing HLA A3 and/or A30 allotypes. The aim of this study was to establish whether such restriction results in the detection of low FHC levels in individuals lacking HLA A3 and/or A30 allospecificities. The FHC mean concentration (+/- SD) in 294 healthy blood/bone marrow donors (HBDs) was 0.24 (+/- 0.2) mg/l. The grouping of HBDs according to their HLA-A FHC product reactivity with one, both or no mAbs did not result in any statistically significant differences (Mann-Whitney test: P > 0.05) between their median FHC concentrations. Since the absence of differences in their FHC levels was not attributable to a difference in the percentage distribution of HLA allotypes associated with high or low HLA-B/C FHC expression, our results indicate that FHC HLA A3 and/or A30 products detected in DDIA by these two mAbs only minimally contribute to FHC serum expression and that the assay is not limited by the failure to detect HLA-A FHC products in A3- and/or A30- individuals.

It is well established that relationships exist between the frequencies of certain HLA antigens and various disease entities. In an earlier study we found a significant correlation between the frequency of HLA-A2 and HLA-A3 and recurrent acute otitis media (rAOM). Of 34 HLA antigens analysed, HLA-A2 occurred in 80.0% and HLA-A3 in only 11.1% of children with rAOM as compared to 55.9% and 27.5%, respectively, in healthy controls. In the present study we investigated the frequencies of the same 34 HLA antigens in 40 children who had been regularly controlled at our clinic for chronic secretory otitis media (SOM) for at least 6 years. HLA-A2 was found in 52.0% (21/40) and HLA-A3 in 27.5% (11/40) of these children, figures on a par with those of healthy controls. The HLA-A2 frequency was significantly lower in chronic SOM patients than in rAOM children. Some other non-significant differences were also found between these two groups. The results indicate a difference in hereditary influence on the pathogenesis of rAOM and that of chronic SOM.

Lymphocytic colitis is a newly described chronic diarrheal disorder. Although its etiology is unknown, the possibility has been raised that autoimmunity may play a role in both lymphocytic and collagenous colitis, a similar clinicopathologic illness. The frequencies of HLA class I and class II antigens were examined in 24 white patients with lymphocytic colitis and in 47 white patients with collagenous colitis. Frequencies in these two disorders were compared to control white populations and to each other. An increased frequency of HLA-A1 was noted in 16 of 24 lymphocytic colitis patients (66.6%) compared with 1089 of 3942 controls (27.6%) (P less than 0.005; relative risk 5.2). Furthermore, HLA-A3 was found in decreased frequency in lymphocytic colitis patients: 0 of 24 (0%) compared with 1017 of 3942 controls (25.8%) (P less than 0.05; relative risk 0.0). Collagenous colitis patients had no significant deviation from control frequencies of HLA antigens. In lymphocytic colitis, there was no significant increase in B8 or DR3 antigens, which are found in linkage disequilibrium with A1 and associated with many autoimmune diseases. Moreover, the frequency of autoimmune-associated class I HLA antigens was not increased in lymphocytic colitis. Statistically significant differences existed between lymphocytic and collagenous colitis in HLA-A1, A3, Bw6, and B7 antigen frequencies. The HLA patterns noted previously in other gastrointestinal disorders, including ulcerative colitis and Crohn's disease, were not apparent in lymphocytic or collagenous colitis. HLA typing provides further evidence that lymphocytic colitis is a distinct form of chronic intestinal inflammatory disease associated with HLA class I phenotypes.

Multiple sclerosis has been shown to be associated with the presence of certain major histocompatibility (MHC) tissue antigens which are coded on chromosome 6. There are racial differences in the antigens associated with MS. The strength of the associations vary in different communities in Western Europe. We have investigated the association between MS and MCH antigens in Northern Ireland in a group of 104 patients. There is a particularly strong association between MS and HLA-DR2, 65.4% compared with 25.5% in 184 controls. A weaker association has been demonstrated with HLA-A3 (44.2% vs 26.5% in controls). There have been conflicting reports concerning an association of HLA-DW2 and HLA-DR2 with a rapidly progressive form of MS. Our data do not support that hypothesis.

HLA-A and HLA-B antigens were determined in 16 unrelated subjects orginating from Veneto affected by idiopathic haemochromatosis (IH). HLA-A3 was found in 13/16 patients vs. 300/1,348 controls (p less than 0.00005). Prevalences of A3,B35 haplotype were 0.4375 in patients vs. 0.0816 in controls (p less than 0.0005). Linkage disequilibrium analysis proved the existence of a positive third-order linkage disequilibrium among IH, HLA-A3 and HLA-B35 alleles. Our data confirm the close association of IH and HLA-A3 and prove the peculiar association of the disease with A3,B35 haplotype in north-eastern regions of Italy. The positive third-order linkage disequilibrium suggests a remote event (mutation, recombination or immigration) as origin for IH and A3,B35 association.