HLA haplotypes in non-familial rheumatoid arthritis.

The frequencies of HLA-A, B, C, DR, and BF haplotypes in 44 unrelated Caucasian patients with definite seropositive rheumatoid arthritis (RA) were compared with haplotype frequencies in controls. Overall, the patients had an increased risk for HLA-DR4, DR3, and DR2 antigens, but frequencies of certain DR4 or DR3 haplotypes were not increased, suggesting the importance of other HLA loci for the evaluation of risk. The presence of DR4 alone was not found to produce an increased risk for RA since the frequencies of certain DR4 haplotypes were similar in patients and controls. Increased frequencies of HLA-B18, DR4, HLA-B15, DR4, and HLA-A1, B8, Cw7, DR3 haplotypes were found in patients. RA susceptibility has been found to be associated with the last two haplotypes in some studies of multiple case families, suggesting that similar genetic mechanisms may underlie the disease in familial and sporadic forms.

HLA antigens and seronegative rheumatoid arthritis.

HLA antigens and clinical features in a series of 46 Caucasian patients (40 females, 6 males) and definite repeatedly seronegative rheumatoid arthritis (RA) of more than two years' duration (mean 11.6 years) were compared with those in 77 seropositive RA patients and 110 controls of the same ethnic and geographic origin. Seronegative RA appeared to be less often erosive than seropositive RA, and seronegative patients had fewer extra-articular features. The frequency of the HLA antigen DR1 was raised in seronegative patients as compared with controls (p = 0.006, relative risk = 3) and with seropositive patients (p less than 0.05). HLA-DR4 was slightly increased in seronegative patients compared with controls (p less than 0.05) but was clearly less so than in seropositive patients (p less than 0.005). Early onset of disease was very significantly associated with HLA-DR1 in seronegative patients (p = 0.007), whereas HLA-DR4 was present more frequently in seropositive patients with onset prior to age 35 (p less than 0.05). No correlation between HLA antigens and intolerance to drugs was found in seronegative patients, whereas in seropositive patients side effects to gold salts were associated with DR3. These results suggest that seropositive and seronegative RA have distinct HLA-DR associations, especially in disease of early onset, in addition to well established clinical differences.

HLA-DR genotype risks in seropositive rheumatoid arthritis.

We studied the distribution of HLA-A, B, C, and -DR antigens in 77 Caucasian patients with sero-positive rheumatoid arthritis. Forty-four patients were genotyped and compared with the control panel of 110 unrelated Caucasian genotyped donors. The data obtained confirm the association of DR4 with RA, and reveal an increased risk of disease for patients carrying DR1, DR2, and DR3, compared to the risk for those carrying other antigens, such as DR5, DRw6, and DR7. There is a higher risk for DR4/4 homozygotes than for DR4/1, DR4/2, or DR4/3 heterozygotes. DR4/5, DR4/6, and DR4/7 have a lower risk than the previously mentioned genotypes. The genotype risks are compatible with the inheritance of a single, linked genetic determinant of disease susceptibility, but we are unable to distinguish between recessive and dominant inheritance of susceptibility using the "antigen-frequencies-amongst-diseases" method. DR4 seems to be more frequent in patients in whom onset occurs before the age of 35 (79% vs. 54% DR4 positive). A significant excess of DR3 + is observed in patients with toxic complications following treatment with gold salts (X2(1) = 8.96).

HLA system and side effects of gold salts and D-penicillamine treatment of rheumatoid arthritis.

Among 67 patients with rheumatoid arthritis treated with gold salts (aurothiopropanol sulphonate) a significant correlation (p less than 10(-2)) was noted between gold toxic reactions, whatever their type, and the HLA antigens A1, B8, Cw7, and DR3. Forty-two patients were genotyped, and a correlation was observed between gold side effects and the haplotype A1 Cw7 B8 DR3 (p less than 10(-2), RR = 8.0). In addition 3 out of 4 cases of renal intolerance to D-penicillamine were observed in patients possessing the Cw7 B8 DR3 haplotype.

[Rheumatoid arthritis and HLA system. A search for correlations between histocompatibility antigens and characteristic features of the disease]. / Polyarthrite rhumatoïde et système HLA. Recherche d'une corrélation entre les antigènes d'histocompatibilité et les caractéristiques de la maladie.

Possible correlations between the HLA antigens A, B, C and DR and the clinical and biological features of rheumatoid arthritis were investigated in 74 patients with positive serology. The DR 4 antigen was present in 46 of these patients (62%), being apparently more frequent in those whose disease had begun before the age of 35 (p less than 0.05). DR 4 was also more common in pure rheumatoid arthritis than in forms associated with Gougerot-Sjogren's syndrome (p less than 0.05). No correlation could be found between the HLA phenotype and the other parameters studied, i.e. sex, corticosteroid therapy. Steinbrocker's radiological stages, plasma levels of rheumatoid factor and gammaglobulins and presence of antinuclear antibodies.

[Rheumatoid arthritis with antinuclear factor. A prospective study of 50 cases (author's transl)]. / Les polyarthrites rhumatoïdes avec anticorps antinucléaires. Etude prospective sur 50 cas personnels.

The clinical and laboratory features of rheumatoid arthritis (RA) with antinuclear factor (ANF) were prospectively analyzed in 50 patients and compared with those of another series of 50 patients of similar age, sex and duration of disease, but without ANF. The severity of articular lesions was about the same in both series, but systemic symptoms and Gougerot-Sjögren syndrome occurred more frequently in patients with ANF. Gold compounds and D-penicillamine appeared to be well tolerated by all patients. RA patients with ANF had more strongly positive responses to latex and Waaler-Rose tests. Farr's radioimmunoassay was sometimes positive (11/49), but as a rule, the degree of positivity was inferior to 50%.

[Treatment of rheumatic polyarthritis with levamisole in 26 patients]. / Traitement de la polyarthrite rhumatoïde par le lévamisole chez 26 patients.

Twenty-six patients with rheumatic polyarthritis (serologically positive) were treated with levamisole at a daily dosage of 150 mg. Treatment was continuous for 3 months and 2 days weekly afterwards. Although improvement may appear from the 1st month onwards, it is more frequent between the 1st and 3rd month (13 good or very good results among the 16 patients still treated) and may even improve afterwards (11 good or very good results among the 11 patients still treated in the 6th month). However, the value of levamisole, which appears to be an active drug against rheumatic polyarthritis, is limited by the frequency of side-effects. In 17 cases the trial had to be discontinued for this reason. The most serious side-effects were of haematological nature (2 leukopenias, 1 thrombocytopenia), but in these patients agranulocytosis was not found.

[Psoriatic rheumatism. Prospective study of 50 cases, without sacroiliac involvement and without rheumatoid factor, compared with 50 cases of rheumatoid arthritis]. / Rhumatisme psoriasique. Etude prospective de 50 cas, sans atteinte sacroiliaque et sans facteur rhumatoïde, appariés à 50 cas de polyarthrites rhumatoïdes

The authors report the results of a prospective study comparing 50 cases of psoriatic arthropathy with peripheral articular involvement only and negative rheumatoid serology with 50 cases of classical or definite rheumatoid arthritis paired according to sex, age and the duration of the disease. The results were studied using the X2 test of statistical significance. Despite frequent similarity with rheumatoid arthritis, psoriatic arthropathy differs from it significantly on the basis of a series of characteristics which may be summarised as follows: less wide dissemination and decreased severity of clinical and radiological articular lesions; more gradual progression by attacks separated by periods of remission, often total, resulting in less severe degree of invalidity than rheumatoid arthritis and therefore requiring less often the use of oral corticosteroids. The authors discuss the case of psoriatic arthropathy with positive rheumatoid serology and that of psoriatic arthropathy with combined peripheral and vertebral column involvement.