Immunogenetic associations of scleroderma-related antinuclear antibodies.

Patients selected for the presence of scleroderma-related antibodies (anti-DNA-topoisomerase I [anti-topo I; n = 43], anticentromere antibody [ACA; n = 63], or anti-Pm-Scl [n = 12]) were studied for class I and class II major histocompatibility complex antigens, as well as for Gm and Km allotypes. Anti-topo I was associated with HLA-DR5 (70% of patients versus 30.6% of controls; Pcorr = 0.0018, relative risk [RR] = 5.3). All patients with anti-Pm-Scl were positive for HLA-DR3 (versus 23.5% of controls; Pcorr less than 0.001); 6 of these patients were DR3/4 heterozygous (50% versus 3.5% of controls; Pcorr less than 0.001, RR = 27.3). Patients with ACA were frequently positive for HLA-DR1, DR4, or DRw8, with 73.7% demonstrating at least 1 of these alleles (versus 41.2% of controls; Pcorr = 0.0152, RR = 4.0). This group of ACA-positive patients who had DR1, DR4, and/or DRw8 consisted mainly of a subgroup of patients with rheumatoid arthritis. We conclude that different class II major histocompatibility complex antigens influence the formation of anti-topo I and anti-Pm-Scl. Important clinical differences between these patient groups and the immunogenetic heterogeneity support the notion of different antibody-defined scleroderma subsets.

Immunoglobulin allotype Gm(1,2;21) in ankylosing spondylitis with peripheral arthritis.

Frequencies of immunoglobulin G (Gm) allotypes were determined in 240 patients with ankylosing spondylitis (AS). The uncommon phenotype Gm(1,2;21) was increased in frequency in 55 patients with AS and peripheral arthritis (14.5% v 3.5% of healthy blood donors; p less than 0.05). In 16 patients with arthritis only of wrist/hand or ankle/forefoot, or both, the Gm(1,2;21) frequency was even higher (31.3%; p less than 0.0005). Patients with AS negative for the HLA antigen B27 (n = 28) differed from the B27 positive patients (n = 205) with regard to the frequency of the Gm(1,2,3;5,21) phenotype (39.3% v 9.3%; p less than 0.0005). These findings support the notion of genetic heterogeneity among patients with AS.

Results of a multicenter placebo-controlled double-blind randomized phase III clinical study of treatment of rheumatoid arthritis with recombinant interferon-gamma.

In a multicenter placebo-controlled double-blind randomized clinical study, 91 patients with rheumatoid arthritis were given 28 days' treatment with recombinant interferon-gamma (50 micrograms daily for 20 days, then 50 micrograms each second day up to day 28, given by subcutaneous injection). The aim of the study was to provide a methodologically clear demonstration of the efficacy of treatment with interferon-gamma, using criteria that could be handled by statistical tests. Evaluatable documentation was available for 79 patients, of whom 40 were treated with the active compound. The principal criterion for the statistical evaluation of the therapeutic success was improvement of the Ritchie "joint pain index" or Lansbury "joint pain index" by at least 30% within 28 days. The chi-square test showed superiority of the interferon arm over the placebo arm with an error probability of alpha less than 1%. In addition, efficacy of interferon-gamma was demonstrated in respect of practically all parameters investigated. The frequency of side-effects, including febrile reactions, was the same for the active compound and the placebo. During interferon treatment the daily maximum body temperature was raised by 0.3 degrees C on average, but was below 37.2 degrees C at all times.

HLA-DR4 and Gm(1,3;5,21) are associated with U1-nRNP antibody positive connective tissue disease.

Patients with U1-nRNP antibodies (n = 35, 31 female, four male) were typed for HLA-A, -B, -C, and -DR antigens and IgG heavy chain allotypes G1m(1), -(2), -(3), G3m(5), and -(21). The patient group was clinically heterogeneous. Four met the American Rheumatism Association criteria for systemic lupus erythematosus, six for progressive scleroderma, and 14 for rheumatoid arthritis. Sicca syndrome was present in seven cases. Twenty three had overlapping features compatible with mixed connective tissue disease (MCTD). Healthy blood donors served as controls for HLA typing (n = 64), Gm typing (n = 228), or both (n = 56). Sixty six per cent of the patients with U1-nRNP antibodies were DR4 positive compared with 28% of the controls (relative risk = 4.9, p = 0.00053). The Gm(1,3;5,21) phenotype was found in 46% of the patients and 25% of the controls (relative risk = 2.47, p = 0.0247). Within the patient group Gm(1,3;5,21) was found only in DR4 positive individuals. The coincidence of HLA-DR4 and Gm(1,3;5,21) increases the relative risk values to 8.0 (compared with the group with neither risk factor). DR4 and Gm(1,3;5,21) primarily seem to be related to U1-nRNP antibody formation and not to disease expression. Patients with or without MCTD did not differ with respect to DR4 or Gm(1,3;5,21) frequency. Disease onset was earlier in patients with HLA-DR4/Gm(1,3;5,21) than in patients without both markers (mean 27.9 v 40.1 years; p less than 0.05).

Results of a phase-II clinical trial on treatment of rheumatoid arthritis with recombinant interferon-gamma.

In an open, non-randomized clinical trial conducted at multiple centres, 49 patients with rheumatoid arthritis were treated with recombinant interferon-gamma for 20 days. The study was carried out in two sub-studies. In the first, the total daily dose of interferon-gamma was 50 micrograms; in the second, 100 micrograms. Of the 49 cases, 40 were evaluable for statistical analysis; 24 of these patients (60%) responded to therapy, according to the criteria of a successful outcome laid down in the study protocol, and were classified as responders. In responders, the clinical parameters investigated improved with both dosages. The lower dosage differed from the higher one in having a markedly lower incidence of side-effects. The results lead to the conclusion that a randomized double-blind phase-III clinical trial should be performed.

Increased frequency of Gm(1,2;21) phenotype in HLA-DR4 positive seropositive rheumatoid arthritis.

Ninety-four patients with seropositive rheumatoid arthritis (RA) were typed for HLA-A, B, C and DR antigens and for immunoglobulin G (Gm) allotypes. Isolated IgG from patient serum was used to avoid interference of IgM rheumatoid factor (RF) with Gm typing in sera with high IgM-RF titer. Besides the association of seropositive RA with the antigen DR4 and an earlier disease onset in DR3/DR4 heterozygotes, we found the uncommon Gm phenotype Gm(1,2;21) significantly more often in our patient group than in healthy controls. Combination of HLA-DR and Gm data shows that individuals with both DR4 and Gm(1,2;21) are at a particularly high disease risk.

[On the question of drug-induced pseudo-LE syndrome: preliminary results in 58 cases (author's transl)]. / Zur Frage einer Induzierbarkeit des Pseudo-LE-Syndroms durch Arzneimittel. Vorläufige Ergebnisse von Erhebungen bei 58 Fällen

Drug intake had been checked in 58 patients with pseudo-LE-syndrome. In view of the findings of the Zürich group a connection between the intake of Venopyronum¿ coated tablets and a pseudo-LE syndrome was strongly suspected in 45. In a further seven patients who also had taken the drug no definite connection could be shown because there was no temporal relationship between drug and disease. Three patients had taken Venopyronum-triplex capsules. Only three patients categorically denied ever having taken the drug in any form.