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The purpose of this study was to test for detectable serum levels of antibodies usually associated with immune-related diseases in children with Vernal keratoconjunctivitis (VKC) and seek for their family history of allergies and autoimmune disorders. The association of human leukocyte antigens (HLA) with VKC was also investigated. We enrolled 181 VKC children and assessed total and specific IgE, antithyroglobulin (AbTG), antithyroidperoxidase (AbTPO), antitransglutaminase (tTG), and antinuclear antibodies (ANA) by standard procedures. Class I and II HLA typing was also carried out following standard protocols, and it was compared with that of healthy subjects. Patients were positive for AbTG (22%), AbTPO (14.6%), and ANA (15.8%), and AbTG positivity was associated with VKC severity (mean ocular score ± SD positive vs. negative: 6.56 ± 2.1 vs. 4.82 ± 2.1; p = 0.03). We found that 12.2% of VKC cases had a positive family history for psoriasis, 6.4% for other cases of VKC, and 5.2% for thyroiditis, while 50.2% of them were atopic. The expression of HLA class I B37 was significantly higher in VKC patients than in controls (7.1% vs. 2.1%, p = 0.04), although not confirmed after multiple antigens testing analysis. Our study suggests a role of common components associated with immune-based diseases in the clinical expression of VKC.

Background Anticoagulation therapy with heparin induces antibodies that recognize multimolecular complexes of platelet factor 4 bound to heparin (anti–platelet factor 4/heparin antibodies). Considering that cardiac surgery induces an intense platelet activation and proinflammatory response, we examined the relationship between formation of anti–platelet factor 4/heparin antibodies and plasma levels of platelet factor 4 and interleukin 6. We also examined the relationship between anti–platelet factor 4/heparin seroconversion and the histocompatibility leukocyte antigen system. Methods In 71 patients undergoing cardiac surgery, anti–platelet factor 4/heparin antibody levels were evaluated by means of enzyme-linked immunosorbent assay preoperatively and 14 days postoperatively. Platelet serotonin release assays were performed to assess the platelet-activating potential of the antibodies. Plasma levels of platelet factor 4 and interleukin 6 were assayed at prespecified time points. Histocompatibility leukocyte antigen status was assessed preoperatively in all patients and was compared with that of 6156 healthy subjects. Results Thirty-seven (52%) patients had anti–platelet factor 4/heparin antibodies with an OD value of 0.45 or greater in 1 or more of the assays. Applying strict seroconversion criteria (>2-fold increase in Optical Density), only 16 (22.5%) patients had evidence of anti–platelet factor 4/heparin antibody seroconversion after the operation. Neither the presence of anti–platelet factor 4/heparin antibodies nor seroconversion influenced postoperative outcomes. The CW4 allele was significantly more frequent among seroconverted patients (46.9% vs 19.1%, P = .002). Platelet factor 4 levels did not influence seroconversion. Patients with anti–platelet factor 4/heparin levels of 0.45 OD units or greater 14 days after the operation had significantly higher interleukin 6 levels measured 1 hour after protamine administration. Discussion Patients with a greater amount of perioperative inflammation could be more likely to have anti–platelet factor 4/heparin antibodies 1 to 2 weeks later. We provide additional evidence that the histocompatibility leukocyte antigen CW4 confers genetic susceptibility in an acquired inflammatory disorder that includes the anti–platelet factor 4/heparin immune response.

The evidence for HLA-Cw antigens' involvement in the modulation of the immune response in bone marrow transplantation, NK alloreactivity and the susceptibility and follow-up for different diseases has been growing in the recent years, but very few data on HLA-Cw distribution in healthy Italian subjects are available to date. This report presents an updated description of HLA-Cw frequencies in Italy, comparing data from the northern (Lombardia) and southern (Campania and Puglia) parts of the country. A total of 1101 healthy subjects of Italian origin were genotyped, and the results showed that HLA-Cw⁎04, Cw⁎07, Cw⁎12, and, in particular, Cw⁎0401, Cw⁎0701, Cw⁎1203, were the most frequent alleles found in all three regions analysed. Nevertheless, statistically significant differences were observed in Cw⁎07 distribution, which was more frequent in the southern than in the northern part of Italy (28.8% vs 22.4%; p = 0.001; OR: 1.4; 95%CI: 1.14–1.73), and in Cw⁎12 distribution, which was more frequent in the north than the south (17.0% vs 12.4%; p = 0.007, OR: 1.4; 95%CI: 1.10–1.91). These results, which give an improved pattern of distribution of HLA-Cw alleles in the Italian population, would be useful in bone marrow transplantation and anthropological studies. Moreover, due to the important role of HLA-Cw antigens in modulation of the immune response and NK alloreactivity, these data would be of interest in studies on susceptibility, follow-up and/or protection against different diseases.

Summary Several studies have emphasized the role of familial factors and familial aggregation in increasing susceptibility to obstructive sleep apnea syndrome (OSAS); the aim of the present study was to investigate the possible influence of human leukocyte antigen (HLA) in the development of sleep disordered breathing and OSAS of children. Between January 2000 and January 2003, all the 370 children [193 males; median age: 5.2 years (range: 1–12 years)] with sleep disordered breathing referred to our Center were screened by a 41-item multiple-choice questionnaire. All habitual snores children underwent a polisomnographic evaluation, and those with an apnea/hypopnea index >3 were diagnosed as having OSAS. All children with OSAS or primary snoring were HLA typied for class I and II. According to nocturnal polygraphic monitoring study, 41 patients were diagnosed as having OSAS and 32 as primary snoring. Patients in the two diagnostic groups were homogeneous for demographic and clinical characteristics. HLA-B65 was found to be significantly more expressed in children with sleep disordered breathing as compared with controls (10.5% versus 3.61; Pypc

Summary No monoclonal antibodies (mAbs) are presently available to measure the total amount of β2-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.

The purpose of this study was to test for detectable serum levels of antibodies usually associated with immune-related diseases in children with Vernal keratoconjunctivitis (VKC) and seek for their family history of allergies and autoimmune disorders. The association of human leukocyte antigens (HLA) with VKC was also investigated. We enrolled 181 VKC children and assessed total and specific IgE, antithyroglobulin (AbTG), antithyroidperoxidase (AbTPO), antitransglutaminase (tTG), and antinuclear antibodies (ANA) by standard procedures. Class I and II HLA typing was also carried out following standard protocols, and it was compared with that of healthy subjects. Patients were positive for AbTG (22%), AbTPO (14.6%), and ANA (15.8%), and AbTG positivity was associated with VKC severity (mean ocular score ± SD positive vs. negative: 6.56 ± 2.1 vs. 4.82 ± 2.1; p = 0.03). We found that 12.2% of VKC cases had a positive family history for psoriasis, 6.4% for other cases of VKC, and 5.2% for thyroiditis, while 50.2% of them were atopic. The expression of HLA class I B37 was significantly higher in VKC patients than in controls (7.1% vs. 2.1%, p = 0.04), although not confirmed after multiple antigens testing analysis. Our study suggests a role of common components associated with immune-based diseases in the clinical expression of VKC.

An ELISA-based double determinant immunoassay has been established to measure the soluble beta2-microglobulin (beta2m)-free heavy chain (FHC) of the HLA-B, -C (and HLA-A3, -A28 and -A30) class I molecular complex in sera from 212 HLA-typed healthy unrelated individuals. FHC was calculated by means of a standard curve constructed using serial concentrations of beta2m-associated HLA-class I heavy chain (HLA-I)/FHC purified from cultured human lymphoid cell C1R-sB7-supernatant. The mean FHC concentration (+/-SD) was 0.25 mg/l (+/-0.2). Its median concentration did not statistically differ between males and females, though the male/female ratio was greater in the high secretor (FHC0.45 mg/l; mean + 1SD) than in the low secretor group (FHC0.05 mg/l; mean - 1SD). FHC0.05 mg/l was statistically (Fisher's exact test) associated with HLA-B17 (p = 0.003); FHC0.45 mg/l was statistically associated with HLA-B35 (p = 0.003) and -Cw4 (p = 0.002). None of these allele-positive groups showed a mean FHC concentration 1.5 times higher than that of the corresponding allele-negative ones. This allotype-dependent HLA-B and C FHC enhancement was less marked than that previously reported for HLA-I in individuals carrying HLA-A9 (and its splits). These results indicate that FHC could be a more valuable marker when its levels are compared among individuals carrying different allotypes. Moreover the lack of correlation between FHC and HLA-I levels measured in 52 HLA-A3, -A28 or -A30 positive individuals suggests that the two molecules may be regulated by different metabolic pathways and their serum expression may have a different biological significance.

We analysed the effect of HLA loci on the secondary sex ratio, and investigated whether allele sharing between parents and between mother and child, or child homozygosity, affected the viability of male embryos, which are generally less resistant to unfavourable conditions during pregnancy. The sharing conditions at the B and DR loci showed significantly differing effects: HLA-B seemed to favour female births, while, in pregnancies subsequent to the first, HLA-DR seemed to favour male births. Both HLA-B and DR loci seemed to work through immunological mechanisms.