Gm and Km allotypes in rheumatoid arthritis.

Immunoglobulin heavy chain (Gm) and kappa light chain (Km) allotype and phenotype frequencies were compared in 173 patients with rheumatoid arthritis (RA) and in 798 controls. No significant differences were found between allotype or phenotype frequencies in overall RA and control groups. However, the Gm(zaxfngb) phenotype and G1m(x) allotype were increased in HLA-DR4 positive RA patients compared with DR4 negative patients and controls, suggesting that immunoglobulin heavy chain genes interact with HLA in the pathogenesis of RA. All four patients with pulmonary fibrosis were Km(1) positive suggesting a possible role for immunoglobulin kappa light chain genes in the pathogenesis of pulmonary fibrosis found in rheumatoid patients.     

Gm and Km allotypes in autoimmune diseases.

The associations or linkages between the polymorphisms of the Gm and Km immunoglobulin allotypes and the susceptibility to autoimmune diseases, including diseases with immuno-pathological pathogenesis are reported in this review. These diseases include multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, insulin-dependent diabetes mellitus, Crohn's disease, coeliac disease, Graves' disease, atrophic thyroiditis, Hashimoto's thyroiditis, myasthenia gravis, chronic active hepatitis, alopecia areata, uveitis, vitiligo, Turner's syndrome, glomerular nephritis, Berger's disease and idiopathic dilated cardiomyopathy. Immunoglobulin allotypes are described as well as the statistical methods used to analyse the data.     

Methacholine inhalation and Gm allotypes in familial asthma

In this paper, we confirmed previous studies where the results showed an incomplete genetic predisposition to allergic asthma. Our results also showed that by using the degree of sensitivity to methacholine and Gm allotypes one can obtain a better characterization than presently available of individual susceptibility to asthma in a familial setting.     

Anaemia in juvenile chronic arthritis

Summary Anaemia is a common manifestation of juvenile rheumatoid arthritis (JCA). We have evaluated 26 JCA patients with anaemia and compared their laboratory parameters to those without anaemia. In the patients with anaemia, activation criteria such as erythrocyte sedimentation rate (ESR) and CRP were significantly higher than in those without anaemia. Anaemia was present in all systemic JCA patients and was present in 42% and 78% of the oligoarticular and polyarticular types, respectively. Serum iron levels and transferrin saturations were low in all, whereas serum iron-binding capacities of the patients were normal. Mean ferritin level was 249pg/l (range 8.46–1000pg/l). There was a significant correlation between ferritin levels and CRP and ESR (r=0.48 and r=0.55 respectively) (both p<0.05). Epo levels were normal. Twelve (60%) of the bone marrow aspiration specimens stained positive for iron whereas 40% stained negative; there were also changes suggestive of myelodysplasia. Sideroblasts were also decreased in number. Thus, in these patients iron is not sufficiently transferred to the erythroid series and/or cannot be used by erythroblasts, accompanied by a possible absolute iron deficiency. Thus we suggest that the iron in JCA tends to be stored in the form of ferritin, not in an accessible form and impaired metabolism along with other factors are effective in the anaemia of JCA.     

Uveitis in juvenile chronic arthritis

About 20% of patients with juvenile chronic arthritis develop uveitis which is frequently bilateral. Risk factors for uveitis are: female gender, pauciarticular onset of arthritis, presence of circulating antinuclear antibodies, and the antigens HLA-DW5 and HLA-DPw2. The visual prognosis in patients with uveitis is good in 25% and fair in 50%. The remaining 25% develop cataract and/or glaucoma. The management of glaucoma is unsatisfactory, but the results of cataract surgery by lensectomy are good.     

Indoprofen in juvenile chronic arthritis

Indoprofen at 10-12 mg/kg body weight was compared with aloxiprin at 80 mg/kg body weight in children suffering from juvenile chronic arthritis. Indoprofen was significantly superior to aloxiprin in reducing soft tissue swelling and joint limitation and was effective in relieving pain and morning slowness and improving grip strength. The drug was well tolerated and is a satisfactory agent for the treatment of chronic arthritis in children.     

DR, C4, and Bf allotypes in juvenile rheumatoid arthritis

HLA-DR, C4, and Bf typing was performed in 99 patients with juvenile rheumatoid arthritis (JRA). DR1 was found with higher frequency in patients with polyarticular JRA than in controls (P less than 0.05). DR3 was more common in patients with fever and/or rash than in those without these manifestations (P less than 0.05). A significant negative association between JRA and C4A6 (P less than 0.05), C4BQ0 (P less than 0.0005), and BfF1 (P less than 0.05) was found. It is possible that a disequilibrium between DR and C4/Bf genes plays a role in the pathogenesis of JRA.     

Gm allotypes and HLA in rheumatoid arthritis patients with circulating antibodies to native type II collagen.

HLA antigens and immunoglobulin heavy chain allotypes (Gm) were determined in 166 unrelated patients with rheumatoid arthritis (RA), 44 of whom had circulating antibodies to native type II collagen. Collagen antibody positive patients showed an association with HLA-DR3 and DR7 (68% compared with 39% of collagen antibody negative RA, p less than 0.005), and with the Gm phenotype, Gm(zafngb). This contrasted with the collagen antibody negative RA patients where there was an association with HLA-DR4 and, in DR4 positive disease only, with the Gm allotype, G1m(x). The Gm(zafngb) phenotype was found in 26% of DR3 or DR7 positive patients overall and only 9% of RA patients negative for these DR antigens (p less than 0.005), suggesting an interaction between HLA-DR3/7 and Gm(zafngb). The differing Gm associations for collagen antibody positive and negative RA provide further evidence for genetic heterogeneity in susceptibility to RA.     

IgG heavy chain (Gm) allotypes in rheumatoid arthritis and in healthy individuals seropositive for IgM-rheumatoid factor

The frequencies of Gm allotypes a, x, f, b, g and n have been investigated in classical seropositive rheumatoid arthritis (RA), erosive definite seronegative RA, non-erosive definite RA and in healthy individuals with serum IgM-RF. No differences in the frequencies of these Gm allotypes were found between patients and healthy controls. It is concluded that any possible putative genes outside the HLA region involved in RA are most likely unrelated to the genes coding for the constant regions of IgG heavy (gamma) chains.     

IgG-anti-IgG antibodies in juvenile chronic arthritis

IgG antiglobulins were measured in 117 children with seronegative juvenile chronic arthritis (JCA). 100 had active disease, and these had significantly higher levels of IgG antiglobulins (mean 0.45 +/- 0.16 micrograms/ml) than the control group (mean 0.25 +/- 0.16 micrograms/ml (p less than 0.01]. The inactive group of patients had a mean of 0.14 +/- 0.06 micrograms/ml, comparable to a group of cord bloods from normal births (mean 0.14 +/- 0.05 micrograms/ml). In the active patients there was no difference when subdivision was made according to their mode of onset into pauciarticular, polyarticular, or systemic.     

Antinucleosome antibodies in juvenile chronic arthritis

A broad range of autoantibodies have been detected in juvenile chronic arthritis (JCA) patients, although, none of them can be considered specific for this entity. Antinuclear antibody (ANA) is routinely searched in these patients mainly because it is associated with uveitis, a comorbidity that is particularly frequent in the oligoarticular form. Nevertheless, the ANA specific antigen target in JCA is unknown. In this study, we aimed to search for antinucleosome antibodies in 30 adult JCA patients and to study possible associations with clinical profile. Ten individuals (33.3%) were positive for antinucleosome antibodies and seven (70%) were simultaneously ANA positive (p?=?0.01). We did not find any significant association among antinucleosome and JCA form, uveitis, age of onset, gender, or functional index. We conclude that in JCA, there is a prevalence of 33.3% of antinucleosome antibodies. Further investigations are needed to understand the ANA positivity found in this disease as far as the clinical impact of this finding.     

Immune complexes in juvenile chronic arthritis

Twenty children with juvenile chronic arthritis (JCA) and two children with SLE were investigated as to the existence of immune complexes in a long-term survey over 24 months. Two different methods were applied, a solid phase C1q RIA and a polyethylene glycol precipitation test. Detection of immune complexes was compared to the course of the disease and other laboratory data. C1q RIA showed a distinctly higher number of positive tests than the PEG precipitation test. The presence of immune complexes appears to be transitory in the course of JCA, as was demonstrated by C1q RIA. A connection with a more advanced stage of the disease is postulated. The positive test can be regarded as a prognostic parameter which, however, cannot be used for the diagnosis of JCA.     

HLA-B27 in juvenile chronic arthritis

The prevalence of HLA-B27 in 88 patients with juvenile chronic arthritis was 22/88 (25%) with little variation among the 3 commonly recognized onset types. This was significantly more frequent than the prevalence of 9.4% in a Danish reference population. A strong association was found between the HLA-B27 antigen and 3 subgroups of patients: (1) boys with pauciarticular and late onset disease; (2) girls with apophyseal joint fusion; (3) a group of patients in whom the clinical picture was compatible with reactive arthritis or incomplete Reiter's syndrome. When these 3 subgroups were excluded from the total patient population, only 8 of the remaining 63 patients carried the B27 antigen, i.e., 13%, which was not significantly different from the prevalence in the reference population. Thus, the 3 subgroups account completely for the increase of B27 in the entire group of patients.     

Microcytic anaemia in juvenile chronic arthritis

The degrees of anaemia and microcytosis in 100 patients with juvenile chronic arthritis (JCA) were analysed according to the pattern of disease and its activity. Microcytosis was common (40% of patients had a mean corpuscular volume (MCV) of less than 75 fl), sometimes severe (MCV less than 65 fl in 14 patients), and closely correlated with the severity of the anaemia. The degrees of microcytosis and anaemia were both directly related to disease activity as measured by the ESR, and were most severe in cases with the systemic form of JCA. In 50 patients iron status was assessed. The serum iron concentration was directly related to the MCV, whereas the serum ferritin was inversely related to MCV and haemoglobin concentration and directly related to the ESR. Bone marrow iron stores were normal or increased in 6 patients with severe microcytic anaemia. These data suggest that the anaemia of JCA is typically microcytic, and that this microcytosis is associated with the disturbance of iron metabolism seen in the 'anaemia of chronic disorders' rather than overall depletion of body iron.     

Immunogenetics of juvenile chronic arthritis in Israel

Typing for HLA-A,B,C and DR antigens was performed in 61 Israeli patients with juvenile chronic arthritis (JCA) and in 120 unrelated controls. No significant associations were apparent in the overall patient group. DR5 was significantly increased in the non-Ashkenazi patients with pauciarticular onset of disease. The only three DRw8 positive patients in the study had pauciarticular onset. DR5 and DRw8 were found in 9 of 10 patients with age of onset less than 3 years. Increased frequencies of Bw50 and Cw6 were observed in patients with systemic onset. Typing for properdin factor (Bf) and glyoxylase (GLO) was carried out in 45 and 50 of the patients, respectively. No associations with alleles of the complement Bf system or the HLA linked GLO system were evident. The confirmation in the ethnically distinct Israeli population of the previously described association of DR5 with pauciarticular JCA suggests that this gene may be closely related to the disease susceptibility gene.     

IgG heavy chain (Gm) allotypes in ankylosing spondylitis

Summary A comparison between 70 patients with ankylosing spondylitis and 97 controls revealed no significant differences in Gm allotypes. In the patients, no association was found between Gm types and various clinical features.