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Serological studies have demonstrated that lichen ruber planus is associated with the HLA-DR1 antigen. This association was also confirmed by us in the Sardinian population. To establish which DRB1 molecular alleles are involved, we studied a selected group of 14 DR1 positive patients affected by cutaneous idiopathic lichen planus and a group of DR1 positive healthy controls using PCR with sequence-specific primers (PCR-SSP). Comparisons between the allele frequencies in patients and controls showed a positive association with cutaneous idiopathic lichen planus for the DRB1*0101 allele (RR = 5.8, P = 0.0097), DRB1*0101 and DRB1*0102 are associated with the same DQA1 and DQB1 alleles and are different only for two amino acids in positions 85 and 86 of the DRB1 gene. In our case report predisposition to cutaneous idiopathic lichen planus is correlated with a valine in position 85 and a glycine in position 86 at the second exon of the DRB1 gene.

A 16-year-old Sardinian girl affected by homozygous beta-thalassaemia was submitted to allogeneic BMT using an HLA-identical, MLC-negative, unrelated donor. The donor and the patient were homozygous for the entire extended haplotype A30, Cw5, B18, F130, DRB1*0301, DRB3*0202, DQA1*0501, DQB1*0201 and heterozygous for DPB1*0301/DPB1*0202. The conditioning regimen consisted of 14 mg/kg busulphan and 160 mg/kg cyclophosphamide. Engraftment was achieved 14 days from BMT and the haematological reconstitution was complete without any signs of acute or chronic GVHD. Seven months after the transplant the patient was in excellent general condition. The hypothesis is advanced that when two HLA extended haplotypes are shared by donors and recipients, particularly in homozygosity, this is a very favourable immunogenetic condition in unrelated BMT.

The HLA-B49 DR4 haplotype, which is rare in Caucasoid populations, has a frequency in Sardinia of approximately 6% and a very strong linkage disequilibrium (LD). To better understand its genetic structure, the Bf, C4A and C4B Class III alleles were studied in 56 healthy unrelated Sardinian subjects of B49 DR4 phenotype and in 24 of their families. Moreover, 14 sick subjects with the same phenotype were examined together with five of their families. A group of 285 haplotypes belonging to randomly selected individuals was used as a control population sampling. The distribution of the Bf, C4A and C4B alleles among the healthy probands revealed two main groups of association: one major group of 36 subjects (64.3%) with the BfF, C4A3 and C4B4 alleles and one minor group of 14 subjects (25%) with BfS, C4AQ0 and C4B1. A similar subdivision was also observed in the small group of patients. The family analysis confirmed these results and showed two different B49 DR4 extended haplotypes: one with the F34 complotype in 79.1% of the probands (delta x 1000 = 49.0) and the other with the S01 complotype in 20.8% of the probands (delta x 1000 = 17.3). The first one, in LD with the A1 and Cw7 alleles, has not yet been reported in other populations. The second one seems to be identical to a haplotype already reported in the Spanish population. The molecular analysis of the DRB1 locus carried out in 20 of the 70 probands demonstrated that, in both haplotypes, DR4 was represented by the DRB1*0405 allele.(ABSTRACT TRUNCATED AT 250 WORDS)

A 25-year-old woman with AIDS was submitted to HLA-identical allogeneic BMT after cytoablation with busulphan and cyclophosphamide and combined anti-HIV-1 therapy with zidovudine, IFN-alpha 2 and anti-HIV-1-specific T cell clones. Marrow engraftment occurred after 18 days and tests for HIV-1 were negative after 30 days but the hematologic reconstitution of the patient was poor. A second BM infusion from the same donor was ineffective and treatment with GM-CSF only induced a transient increase of the blood cell count, suggesting iatrogenic damage to the BM microenvironment. The development of ARDS led to the death of the patient 10 months after transplantation. Post-mortem investigation did not reveal any active infections and PCR on autopsy tissues was negative for HIV-1.

With the aim of searching for HLA haplotypes and non-B27 allele frequency variations in Sardinian AS patients, HLA-A, B, Cw, DR, DQ and Bf, C4A and C4B typing and haplotype assignment was carried out in the families of 25 AS patients and in 44 healthy individuals, all B27 heterozygotes. In the AS patients a significant increase of the A2, Cw2, B27, DR2, DQ1 haplotype was found. This depends only partially on the linkage disequilibrium existing in the Sardinian population between B27 and the other alleles of this haplotype, and rather seems to be due to a primary association of Cw2 and DR2 alleles with AS. Preliminary data seem to show that this haplotype bears the S31 complotype and the DRB1*1601 allele both in the AS patients and in the healthy controls. The pathogenetic implications of these findings are discussed.

A study on the HLA structure of the Sardinian population was carried out on 551 healthy unrelated families representing all of the island districts. Altogether 2202 HLA-A, B, Cw, DR individual haplotypes and 853 different haplotypes were determined. Cavalli-Sforza and Edwards' genetic distance index for the total of 62 tested alleles showed a modest heterogeneity between one district and another (0.09-0.16). The genetic distance between Sardinians and the rest of the Italian population was 0.23 (0.22-0.26) and progressively increased in comparisons with caucasoids (0.26), negroids (0.34) and mongoloids (0.41). Sixty-three two-locus haplotypes with a high positive linkage disequilibrium were observed in our family sample. The percentages of two-locus haplotypes in LD shared with other populations turned out to be 45% with caucasoids, 20% with negroids and 10% with mongoloids. The distribution of the A, B, Cw, DR haplotypes is shown with 673 of them represented only once or twice, and 10 (1.2%) 14-322 times each. Of the latter, 8 are extended haplotypes, 6 of which characterize the Sardinian population. The analysis of our data suggests that the present-day Sardinian population is the result of a superposition of different populations, mainly consisting of caucasoids on a pre-caucasoid paleo-Mediterranean substratum.

479 families, each with a proband affected by homozygous beta-thalassemia, were typed for HLA. 224 families with a total of 1020 members were typed for the HLA-A, B, C, DR and DQ loci and 255 families with 1046 family members, were typed for the HLA-A, B, and C loci. Altogether, 896 A, B, C, DR and DQ haplotypes and 1020 A, B and C haplotypes were defined. At the same time, 120 healthy unrelated individuals from the same population were typed and used as controls. The analysis of the results was carried out at antigen, allele, haplotype, genotype and sex ratio level with the aim of looking on the one hand, for the existence of heterogeneity between the probands, the unrelated individuals and the healthy siblings and, on the other, for the existence of any distortion whatsoever of the HLA segregation in either the probands or in the healthy siblings in respect of the expected values according to the Mendelian equilibrium. No significant differences were evident between the probands and the controls by the tests carried out at different levels of the HLA system. This leads us to exclude the existence of an association between beta-thalassemia and HLA in the population studied. Moreover, the analysis of the transmission of the alleles, the haplotypes, the genotypes and the sex-ratio by parents to both affected and to healthy children did not show any clear evidence of segregation distortion in respect of the theoretical values.

HLA Class I and Class II antigens were studied in 103 unrelated Sardinian patients with Graves' disease (GD), 71 of whom had ophthalmopathy, and in 220 healthy controls. Molecular typing of the DQB1 allelic variants was carried out on 34 GD patients and 35 healthy controls, selected for the HLA-DR2-DQw1 phenotype. The results of the serological typing showed a positive association with the DR2 and the DQw1 antigens and a negative association with DR3 and DQw2 antigens. These associations were stronger in the GD patients with ophthalmopathy. The DQB1 molecular analysis in patients with the HLA-DR2-DQw1 phenotype revealed the presence of the DQB1*0502 allele in 91.1 per cent of the patients and in 82.2 per cent of the controls. In the Sardinian population GD seems to present a different HLA association than that observed in other Caucasian populations (DR3-Dw24). The DR2 and DQw1 positive associations may be explained by the high frequency of the DQB1*0502 allelic variant (37.7 per cent) which is rare in the other Caucasian populations. The absence of an association between DR3 and GD in Sardinia can be attributed to the very low frequency of the HLA-B8-DR3 (Dw24) haplotype. In fact, in the Sardinian population, DR3 is associated with the allelic variant Dw25 carried by the HLA-B18-DR3 haplotype.

Background: In this work we investigated whether serologically HLA class II compatible donor-recipient pairs showed differences in restriction fragment length patterns, and whether there is a correlation between the genomic differences observed and the incidence of rejection and acute graft versus host disease (GVHD)., Methods: High molecular weight DNA was extracted from thirty-three transplanted thalassemic patients and from their genotypically HLA identical donors. The DNA was digested with TaqI and PstI restriction enzymes, separated by horizontal electrophoresis and transferred onto nylon filters., Results: Differences at the molecular level were observed in only one patient, who rejected the transplant respect to his donor when DNA was digested with the TaqI restriction enzyme and hybridized with DPB cDNA probe., Conclusions: Although the molecular analysis revealed a difference between a patient who rejected the transplant and his donor, the RFLP typing confirmed the serological identity of the HLA class II antigens in all the other donor-recipient pairs studied.

This study was carried out in Sardinia, an Italian region with a very high IDDM incidence. HLA class I and class II antigens were studied in 97 unrelated IDDM patients, 33 complete families with at least one affected member each, and 559 healthy controls. Molecular typing of the DQB1 alleles was carried out in 31 patients and 61 controls. The haplotypes were determined by family studies. The HLA-DR3, DQw2, and DR4 antigens were positively associated with IDDM. The DR3 antigen was nearly always associated to B18 and frequently carried by the extended haplotype A30 Cw5 B18 3F130 DR3 DQw2. The genotype analysis of the patients showed a strong increase of the DR3/DR4 heterozygotes with a relative risk higher than that of the DR3 and DR4 homozygotes. The DR2 antigen was negatively associated with IDDM in the central island districts but not in the southern districts. The DQB1 molecular analysis showed only three alleles in the patients: DQB1*0201 (75.8 per cent), DQB1*0302 (16.1 per cent), and DQB1*0502 (8.1 per cent). These alleles are non Asp 57, so it would seem that nearly if not all Sardinian IDDM patients are NA/NA homozygotes. The DQB1*0502 allele, extremely rare in other Caucasian populations, represents in Sardinia about 70 per cent of the HLA-DR2 haplotypes, contributing to the increase of the pool of IDDM susceptible genes. Moreover it is carried in 27 per cent of the DR2 positive individuals with the extended haplotype A2 Cw7 Bw58 3F31 DR2 DQw1.AZH.

A 12-week trial was carried out to compare the efficacy of pirazolac (300-600 mg b.i.d.) with that of indomethacin (25-50 mg t.i.d.) in patients with ankylosing spondylitis. A total of 119 patients completed the treatment period, with 32 drop-outs. Both therapies showed significant improvements in clinical symptoms.

We report a case of classical Kaposi's sarcoma (KS) in a patient affected by B-cell chronic lymphocytic leukemia for 2 years and who had not received any antiblastic treatment. At the ultrastructural analysis the leukemic cell showed rather immature features, and the immunologic phenotype (absence of detectable cytoplasmic Ig, and expression only of the DR, B2 and IgD lambda molecules on the surface membrane) proved its intermediate level of maturity, its monoclonality and relative rarity. The patient presented a complex immunologic deficiency, revealed not only by the monoclonality of the B lymphocytes and their low degree of maturity, but also by the almost total absence of T helper lymphocytes, by the high reduction in NK activity, by the very scarce proliferative response to the polyclonal mitogens PHA, ConA and PWM, and by a complete anergy to the skin test of delayed reactivity. The search for antibodies against the viruses EBV, CMV, HTLV-I and HTLV-III in the serum was negative. At the HLA typing, the patient was DR5, as are most classical KS and/or B-CLL patients. The data are discussed in relation to documented non-casual association between B-CLL and KS. We stress that immunosuppression may play an important role in the pathogenesis of both diseases and the possibility of their being conditioned by common genetic HLA-associated factors of predisposition.

The presence of HLA-associated genetic factors in patients with multiple skin carcinomas was investigated. 43 patients affected by multiple basal and squamous cell carcinomas and 220 healthy age-matched controls were typed for 72 HLA-A, B, C, DR antigens. A negative association of B-17 (mostly B-58) and a positive association of Cw-3 and DR-1 was observed in patients with multiple basal cell carcinomas; a similar negative association with B-58 and positive association with DR-1 was seen in patients with squamous cell carcinomas. The results of this study suggest the presence of resistance factors to the development of skin cancers associated with B-17 (B-58) antigen.

Familial mediterranean fever (FMF) is an hereditary disorder characterized by attacks of febrile serosal inflammation involving pleura or peritoneum and synovium, followed usually by insidious onset of amyloidosis. In other patients amyloidosis of AA-type is the only finding of the disease. This disorder is common in Jews of Sephardi and Ashkenazi ancestry, Arabs, Armenians and Turks. In this work the clinico-biological features and the therapeutical aspects of a patient, suffering from FMF, of Italian ancestry are presented.

T lymphocyte subsets, mitogenic response, and immunoglobulin levels were studied in peripheral blood from 95 thalassemic patients before and at different times after bone marrow transplantation. With the exception of patients receiving more than 100 transfusion units before transplant, who showed an increased percentage of CD8-positive cells, thalassemic patients were essentially immunologically normal. Depressed lymphocyte proliferative response to phytohemagglutinin, concanavalin-A, and pokeweed mitogen; decreased IgG, IgM and IgA levels; and abnormal T subpopulation distribution were observed early after transplant. Long-term transplanted patients showed complete recovery of the immunological profile with the exception of the IgA levels, which were significantly decreased up to 2 years after transplant.

Twelve Sardinian patients affected by histologically defined classic Kaposi's sarcoma (KS) were HLA-A, B, C and DR typed. Compared to 220 age and ethnically matched healthy controls, KS patients showed a significant increase in HLA-DR5 (66.6 vs 23.1%, P less than 0.001) and a considerable decrease in HLA-DR3 (8.3 vs 53.6%, P = 0.0055). No definite association was observed for other HLA antigens. These results confirm the existence of an HLA associated genetic control of KS susceptibility and support the hypothesis that HLA-DR5 plays the role of a predisposition marker while HLA-DR3 bears a genetic resistance to the disease.

Increased iron storage represents a characteristic condition in patients with beta zero-thalassaemia intermedia. Iron overload is an important factor in cellular damage. Recent studies have shown an enhanced lysosomal fragility due to increased iron storage. 13 patients with beta-thalassaemia intermedia, aged 17-44 years, were studied. Both serum ferritin and serum N-acetyl-beta-D-glucosaminidase levels were evaluated in all subjects studied. A significant linear correlation (P less than 0.05) between serum ferritin and serum N-acetyl-beta-D-glucosaminidase levels were found.

The genomic DNA of 25 unrelated individuals with HLA haplotype A30 Cw5 B18 BfF1 DR3 D w52 DQw2 was digested with the restriction enzyme Taq I and hybridized with cDNA probes for C4 and 21-OH genes. Eighteen individuals and a non-Sardinian reference cell (DUCAF) were homozygous for the entire extended haplotype, six individuals were heterozygous for the HLA-A locus and homozygous for the rest of the same haplotype. All of the 18 homozygous individuals, four of the six heterozygous subjects and the DUCAF cell revealed the absence of two fragments at 3.2 and 2.4 kb corresponding to the 21-OH A gene, and the absence of fragments corresponding to the C4 B "long" or "short" gene. The contemporary absence of the 21-OH A and C4 B genes seems to be a constant characteristic of this extended haplotype in the Sardinian population and suggests that this and other extended haplotypes bearing C4 A or C4 B null alleles could be ancestral haplotypes which never duplicated at these loci.