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Tat protein may activate helper CD4+ cells in individuals infected with HIV type 1 (HIV-1). This protein is a regulatory protein that is necessary for replication of HIV-1. A study examined response of helper CD4+ T cells to recombinant (genetically engineered) Tat protein and 12 different Tat protein subunits in 15 HIV-positive individuals and 11 HIV-negative individuals (control group). HIV-positive individuals were more likely to have a response to recombinant Tat than those in the control group. Three Tat protein subunits caused a helper CD4+ T cell response in the HIV-positive individuals but not in HIV-negative individuals.

Infection with beta hemolytic streptococci may be less likely to cause rheumatic fever than other types of reactive arthritis in adults. Rheumatic fever is one type of reactive arthritis caused by this type of bacteria. A study examined 76 adults with an arthritis syndrome or increased severity of a chronic rheumatic disease. All the patients had a simultaneous rise in blood levels of antistreptolysin O (ASO). ASO is an antibody that inhibits streptolysin, a toxin produced by group A streptococci. None of the patients were diagnosed with classic rheumatic fever despite elevated blood levels of ASO. Twenty-six patients were diagnosed with arthritis in association with a known rheumatic disease, 25 with non-specific joint and muscle pain, 20 with reactive arthritis and five with septic arthritis.

Screening of donor-specific antibodies or alloantibodies after kidney transplantation has not been performed routinely. The aim of this study was to evaluate the humoral antidonor and alloresponse of immunologically low-risk recipients of cadaveric renal allografts during the first posttransplant year.

Several studies indicate an association between human leukocyte antigens (HLA) and clozapine-induced agranulocytosis. The authors have previously reported a significantly increased frequency of HLA-A1 among patients with schizophrenia who do not respond to conventional drugs, but do respond to clozapine treatment. In this study, the authors addressed the question of whether the same association is found in patients developing granulocytopenia or agranulocytosis. The frequency of the HLA-A1 allele in patients with clozapine-induced agranulocytosis or granulocytopenia was low (11.5%), whereas HLA-A1 was associated with a good therapeutic response to clozapine at an allele frequency of 58%. The frequency of HLA-A1 is 20% in the Finnish population. These results suggest that HLA-A1 may predict a good therapeutic outcome and a low risk of agranulocytosis and, thus, enable defining a subgroup of patients with schizophrenia in whom clozapine treatment could be started early to stop the disease from progressing.

AbstractThe purpose of this study was to investigate the clinical relevance of conversion of post‐transplant T cell crossmatch between kidney donor and recipient. This study comprises 892 cadaveric renal transplantations performed on 874 adult patients between August 1991 and December 1997. Recipient selection was based on a negative complement–dependent cytotoxic T cell crossmatch test with current (2 months old) serum. For this study, on day 0 and day 14 after transplantation, serum samples were collected for later crossmatching. On day 14 after transplantation, the crossmatch had converted to positive in 76 transplantations (8.5%). Acute rejection occurred in 50 % of the converters and 22 % of the non‐converters (P< 0.005), and graft survival was significantly poorer (P< 0.025), being 85 vs 94% at 1 and 68 vs 83 % at 5 years, respectively. In patients with delayed graft function, 1‐year graft survival was 77 % in the converters and 91 % in the non‐converters (P< 0.05). Conversion of T cell crossmatch, especially in connection with delayed graft function, identifies a subgroup of patients at high risk of severe rejection and poor graft survival.

A group of 151 cytomegalovirus (CMV)‐seropositive renal transplant recipients was retrospectively evaluated. CMV disease was verified in 16% of the patients 2 to 24 weeks posttransplant. The 1 year survival rates of the patients and the grafts were not impaired by CMV. Antigens in locus HLA‐B5 in the recipient and HLA‐A3 in the donor were demonstrated to be associated with an increased incidence of posttransplant CMV disease.

The association of an early steroid-resistant rejection (SRR) with HLA-DR antigens was analyzed in 410 kidney transplantations. A severe SRR leading to a poor (45) 1-year graft survival (GS) occurred in 22 transplantations (5). An acute reversible rejection (ARR) with a GS of 94 was found in 80 transplantations (20). For the 308 (75) transplantations with no early rejection episodes the GS was 91.

Summary: Twenty-one families, each with two diabetic children, from North Finland were HLA typed. The grade of HLA identity between diabetic siblings was evaluated, and frequencies of various HLA antigens in familial cases were compared to those of non-familial cases from the same area. Ten pairs of diabetic children were HLA-identical and eleven haploidentical; two of the latter were identical for the HLA-D locus. These figures emphasize the significance of HLA-region associated genetic factors in the susceptibility to the disease, but do not support a simple dominant/recessive gene theory. There was a significant difference between familial and non-familial IDDM cases in the frequencies of B15, Bw16, B40 and Cw3 antigens. Bw16 was greatly increased and B15, B40 and Cw3 decreased among familial cases. The haplotype A9, Bw16 was common in familial cases, but, compared to healthy controls, the frequencies of the two antigens were also slightly increased among non-familial cases. Neither Dw3 nor Dw4 was associated with Bw16 antigen. The differences between familial and non-familial IDDM cases and the significance of the A9, Bw16 combination in the patients emphasize the heterogeneity of IDDM.

Gold salt therapy-induced pneumonitis is a rare complication in patients with rheumatoid arthritis (RA). We studied HLA-A, B, C, D/DR, and complement factor B (Bf) and C4 alleles in 17 patients with RA and gold-induced pneumonitis and found that these patients had strikingly homogeneous major histocompatibility complex (MHC) markers. Eight of them (47 percent) had the alleles HLA-A3 B35 Dw1 BfF C4A3,2 (BO) which were shown by family studies of some patients to be inherited as an extended MHC-haplotype with an apparent gene duplication in the C4A locus. The other high-risk phenotype, HLA-B40 with a C4 null allele, was found in eight patients (47 percent.) All but three of the 17 patients had at least one of the two high-risk markers, the frequency of these combinations being clearly higher than in the two control groups: patients with RA but with no gold-induced side effects and healthy individuals. Our study shows that use of several MHC markers together results in a strong association between the markers and the disease.

HLA antigens were examined in 118 unrelated patients of whom 49 had definite severe systemic lupus erythematosus (SLE). HLA A1 was found in 45% of the 49 SLE patients and in 20% of the controls, which consisted of 900 blood donors. HLA B8 was found in 47% of the patients and in 20% of the controls (relative risk=3.5, P=0.000017), while HLA B7 was found in 22% of the patients and in 24% of the controls.

• The role of HLA and complement genes was studied in 13 patients with subacute cutaneous lupus erythematosus by combining the major histocompatibility complex class I (HLA-A, -B, and -C), class II (HLA-DR), and class III (properdin factor B [BF] and C4) phenotyping with DNA level analysis of the C4 region. Of our patients, 54% had DR2 antigens and 50% had DR3 antigens, when the frequencies in the controls were 25% and 33%, respectively. The DR3 antigen was associated with annular skin lesions that were associated with a younger age at onset, whereas the DR2 antigen was associated with papulosquamous skin lesions and an older age at onset. The frequency of C4 null alleles was 83% in the patients and 50% in the controls. The null alleles were found in both C4A and C4B loci and were not associated with any special major histocompatibility complex haplotype. The DNA studies showed that the null phenotype mostly resulted from a gene deletion. A highly increased frequency of complement C4 null alleles may be a predisposing factor for cutaneous lupus erythematosus and especially of the subacute cutaneous type.(Arch Dermatol. 1989;125:791-796)

Eighteen patients with juvenile autoimmune thyroiditis were studied. At diagnosis 8 (44%) of the patients were euthyroid and 10 hypothyroid, whereas at the end of 6 to 12 months follow-up, 12 (66%) were euthyroid and 6 hypothyroid. All the patients were HLA-typed. The frequency of HLA-DR4 was increased in the patients when compared with the normal population, 63 vs 28% (p < 0.01). An analysis of thyroid-infiltrating mononuclear cells revealed that the majority of the thyroid-infiltrating lymphocytes were T cells. More T lymphocytes and fewer B lymphocytes and HLA class II positive lymphocytes were found among the thyroid-infiltrating mononuclear cells in euthyroid than hypothyroid patients. The numbers of thyroid-infiltrating B lymphocytes correlated with the levels of thyroid microsomal antibodies. No correlation was found between thyroid function and thyroid antibodies.

• The problems of differentiation between environmental and genetic influences on the development of multiple sclerosis are well known. Twin studies may provide valuable information on this question. However, most published twin series are selected and no thorough clinical twin studies based on epidemiologic series have been carried out. In this study, all available same-sex twin pairs with clinically definite multiple sclerosis derived from the Finnish Twin Cohort of 15815 pairs were studied by clinical evaluation, magnetic resonance imaging, and visual and auditory evoked responses. The mean length of follow-up of the pairs after the onset of symptoms of multiple sclerosis was 20 years. Two of the seven monozygotic pairs were concordant; one was definitely so, and in the other, the co-twin of the index case had, in addition to clinical findings, white matter changes suggestive of multiple sclerosis in magnetic resonance imaging and abnormal visual evoked responses. All six dizygotic pairs were discordant. The frequency of the HLA antigen DR2 in probands (69%) was significantly increased, but the distribution among the healthy subjects and patients showed nonsignificant differences. The results indicate a genetic influence on the susceptibility to multiple sclerosis, although still unknown genetic determinants are possibly involved.

To determine the hereditary pattern of acute anterior uveitis, we examined seven families—one family with four cases, one family with three cases, and four families with two cases of acute anterior uveitis. A total of 16 patients with uveitis and 28 relatives underwent ocular examinations and serologic determination of HLA antigens, protease inhibitor α1-antitrypsin typing, and X-ray examination of sacroiliac joints.

After separating the *F and *S alleles by electrophoresis the allele-specific hemolytic activity was detected by agarose overlay method using the programmable densitometer for scanning. The hemolytic activity of BF allotypes was analyzed from 81 individuals. In thirteen FS heterozygous serum samples BF F had lower hemolysis than BF S. Four FF homozygous samples also exhibited lower hemolysis than a homozygous control sample. The low hemolytic activity of F in FS heterozygotes was not due to decreased protein concentrations relative to S. On the contrary, BF F was associated with higher protein concentration than BF S. The relative quantitation of the allele specific BF protein was done by crossed immunoelectrophoresis. BF F with low hemolytic activity but with high protein concentration associated strongly with HLA B35 phenotype and the family material confirmed the association with the haplotypes A3, Cw4, B35, DR1, BFFB, C4A3BQO (or A2BQO, A3,2BQO). The results suggest that particular MHC haplotypes contain a factor B allele with encoding for poor hemolytic activity or that MHC haplotype specific regulatory elements affect pre- or post-translational activity levels.

Congenital heart block without intracardiac anatomic malformations is a potentially lethal disease affecting children and newborns. The mother often has an autoimmune disorder with autoantibodies against SS‐A/Ro and/or SS‐B/La antigens. However, only a minority of the children of these mothers develop complete heart block. It is believed that the maternal antibodies are pathogenic, but other immunological mechanisms such as cell‐mediated injury cannot be excluded. Maternal cells may recognize fetal antigens adjacent to fetal HLA, and thus some children may be more susceptible to heart block than others, depending on their HLA genetics. The purpose of this study was to evaluate whether there are HLA differences between children with heart block and their healthy siblings. Six affected children in four families and their siblings were studied. MHC class I were typed serologically and class II and some non‐HLA alleles were typed by DNA techniques. DQB1*03/04 were seen more often in the affected children than in the siblings. Some other differences were also seen in the other antigens of the MHC area.

We carried out a prospective study on clinical variables and functions of polymorphonuclear leukocytes (PMNs) of 20 patients with early rheumatoid arthritis (RA) and compared the results with the presence of erosions before treatment and at a one-year follow-up. Migration of PMNs determined by agarose and filter assays and respiratory burst of PMNs determined by luminol-enhanced chemiluminescence (CL) test were studied both before starting RA-modifying treatment and 6–12 (mean 7.3) months later. PMNs of the patients without erosions at one year, as compared to the patients with erosions, showed significantly depressed migration into filter and significantly depressed CL responses toN-formyl-methionyl-leucyl-phenylalanine, both before starting the treatment and at 7.3 months. Although causality remains uncertain, the results suggest that depressed functional capacity of PMNs is associated with low risk of joint destruction in early RA.

The anti-hapten response of mice to xenogeneic, allogeneic and syngeneic hapten-erythrocyte conjugates was studied. The amount of anti-hapten antibody produced was proportional to the degree of conjugation when xenogeneic cells were used. Densely conjugated cells induced antibody approximately 50 μg/ml of which 80% was 7S type. Allogeneic and syngeneic erythrocyte conjugates were also immunogenic. They caused a response of which l/3 was 7S antibody. Thymectomy did not affect the response to syngeneic lightly coupled conjugates at all and the response to highly coupled cells only partially. When allogeneic and syngeneic cells were employed, the amount of antibody produced was not proportional to the degree of conjugation. Very lightly conjugated cells were more immunogenic than more highly conjugated ones. The lightly coupled cells were shown to survive in the circulation while the highly coupled ones were rapidly cleared.

WE have isolated numerous variants of a mouse myeloma cell line which synthesised altered heavy immunoglobulin chains and normal light chains after treating the line with the acridine mustard ICR-191 (refs 1–4). The four types of primary variants that we found are shown in Table 1. The primary variant clones were generally stable but we did find one clone which on recloning produced subclones synthesising a variant heavy chain with molecular weight lower than that synthesised by the primary clone. This observation raised the question of whether certain primary variants might have a built-in instability and that the original mutation might be affecting a regulatory process. We were thus led to seek additional examples of spontaneous secondary variant production to see if this were a more general phenomenon. Here we report our results.

Defects in the enzyme steroid 21-hydroxylase (21-OH) result in congenital adrenal hyperplasia (CAH), a frequent disorder of steroid biosynthesis. The gene encoding the enzyme, 21-OHB, has been mapped adjacent to the complement component C4B gene in the human HLA gene complex. DNA-level analyses of patients with CAH have shown that the 21-OHB gene has often been deleted, but the detection of 21-OHB delections in heterozygotes is often problematic because it is based on relative band intensities. We here report a DNA polymorphism in the C4A91 gene unique to one particular type of 21-OHB deletion occurring solely with a complement phenotype BfF C4A91 B null, shown earlier to be frequent in CAH patients. This marker makes direct detection of the 21-OHB deletion in heterozygotes possible.