HLA-DRB1* GENE SEQUENCES IN HLA-DR4 POSITIVE AND NEGATIVE PATIENTS WITH RHEUMATOID ARTHRITIS

The second exon of the DRB1 gene encoding for the first domain of the HLA-DR β-chain was sequenced in 16 patients (10 DR4/DR1 positive, 6 DR4/DR1 negative) with seropositive rheumatoid arthritis (RA). We could confirm the strong association of susceptibility to RA with functionally equivalent conformations on otherwise distinct MHC molecules. At least one HLA-DR allele in all of the analysed DR4 or DR1 positive patients showed such an epitope with a minimal variability limited to residue 71. However, in HLA-DR4 and -DR1 negative patients such a similar epitope could not be detected.     

HL-A ANTIGENS IN JUVENILE RHEUMATOID ARTHRITIS

HL-A antigens were examined in sixty-two patients, thirty-one boys and thirty-one girls, diagnosed as having JRA. HL-A 27 was the only antigen with a significantly increased frequency. This increase concerned predominantly male patients in whom the disease developed at the beginning of puberty. In this group of sixteen boys, the polyarticular form was more frequent and tended to be associated with sacroiliitis, while the rheumatoid factor was negative in all but one. The frequency of HL-A 27 in this group was 62.5%. The patients were also examined by the lymphotoxic test with anti-H-2 allo-immune sera known to exhibit a high degree of association with some HL-A antigens. On JRA lymphocytes these associations were confirmed for HL-A 2 and anti-H-2^f and for HL-A 27 and anti-H-2^p. The strongest reactions were observed with lymphocytes from male patients around the age of puberty. These data indicate that steroid hormones influence the expressivity of some HL-A-associated cell plasma membrane structures.     

T CELL RECEPTOR DELTA LOCUS POLYMORPHISM IN RHEUMATOID ARTHRITIS

In order to identify new susceptibility markers for Rheumatoid Arthritis (RA), we analysed the dinucleotide repeat polymorphism at the T cell receptor delta locus (TCRD) in 65 RA patients and 99 healthy Belgian controls. A significant under-representation of the A4-A5 TCRD genotype was observed in the RA population.     

幼年类风湿性关节炎患儿细胞及体液免疫的改变

用单克隆抗体测定了１７例幼年类风湿性关节炎患儿外周血中Ｔ淋巴细胞亚群的含量，结果显示ＣＤ３细胞，ＣＤ４细胞及ＣＤ４／ＣＤ８与正常对照组比较存显著性差异，ＣＤ８细胞无统计学意义，提示了幼年类风湿性关节炎存在有细胞免疫功能紊乱，同时还观察到消炎痛治疗本病对Ｔ淋巴细胞亚群无影响，并且观察了血清免疫球蛋白，发现ＩｇＣ高于正常对照组，ＩｇＭ和ＩｇＡ无显著性差异。     

HLA-DR, DP and DQ expression in the small intestine of patients with coeliac disease

Frozen sections of jejunal mucosa from control subjects and patients with both treated and untreated coeliac disease were examined for HLA class II DR, DP and DQ expression. Different staining patterns with monoclonal antibodies to the different class II subgroups were observed with the control subjects. There was some inter-subject variation but in general DR greater than DP greater than DQ staining was observed with the villous enterocytes staining most strongly with the staining decreasing towards the crypt bases. The patients with treated coeliac disease gave a similar pattern to the controls. The patients with untreated coeliac disease generally gave a more intense and relatively uniform staining of both surface and crypt enterocytes for all class II subgroups.     

HLA DQ AND DP IN FINNISH FAMILIES WITH CELIAC DISEASE

We studied DQA1, DQB1, and DPB1 alleles in 31 Finnish families with celiac disease (CD). All healthy first-degree relatives underwent clinical investigation, including in most cases biopsy, to establish whether clinically silent CD was present. Our results indicate that all patients, having either full clinical CD or its silent form, had the susceptibility alleles DQA1*0501 and DQB1*0201. The different clinical outcomes of CD were therefore not directly determined by the DQ alleles. The frequency of DPB1*0101 was also higher in CD patients, but the association appeared secondary to those of DQA1*0501 and DQB1*0201 (DQ2). The primary association of CD with the DQA1*0501 and DQB1*0201 alleles, rather than with HLA haplotypes, was confirmed in multiplex families.     

RHEUMATOID ARTHRITIS WITH SYSTEMIC NECROTIZING ARTERITIS

An autopsy case of rheumatoid arthritis with active polyarthritis, systemic necrotizing arteritis, pleuritis, pericarditis, rheumatoid nodules in a few organs and a healing gastric ulcer was reported. Histologically, systemic necrotizing arteritis was characterized by vascular changes of the following three types: Granulomatous arteritis with a characteristic arrangement of mesenchymal cells forming a palisade around coagulation necrosis of media and some of them formed a rheumatoid nodule-like lesion in the wall (RA type); Fibrinoid arteritis very similar to the Kussmaul-Maier type periarteritis nodosa (PN type); and chronic arteritis with endarterial proliferation (Ep type). Although it is hard to distinguish arteritis of PN type from the Kussmaul-Maier type periarteritis nodosa, arteritis of RA type with rheumatoid nodule-like lesion in the wall may be interpreted as an extremely developed form of vasculitis in rheumatoid arthritis.     

PATHOLOGICAL SYSTEM CONCEPT OF RHEUMATOID ARTHRITIS

Rheumatoid arthritis is a disease of the mesodermal germ layer. It is based on two totally different patho-mechanisms; a) an exudative-inflammatory process, and b) a primary necrosis of various mesodermal tissues. The exudative-inflammatory processes take place in the mesodermal spaces; the primary necrotizing processes occur in the interior of various mesodermal tissues. Whereas the lining cell tissue inflammation is non-characteristic, and the necrosis in rheumatoid arthritis can be taken as specific. The presence of the rheumatoid factor is optional in the lining cell tissue inflammatory processes; it is obligatory in necrosis.
Consequently, rheumatoid arthritis is a disease of the mesodermal germ layer which can occur at two levels. On the first level, the process takes place at the border of mesodermal spaces. On the second level, in which the rheumatic factor is obligatory, the process becomes more complicated, since various kinds of mesodermal tissue structures, including heart muscle and vascular walls, die initially. The clinical picture of rheumatoid arthritis is thereafter characterized by the visceral processes.     

AMYLOIDOSIS ASSOCIATED WITH JUVENILE RHEUMATOID ARTHRITIS

Clinical and pathological findings are reported in a Japanese girl who died of secondary amyloidosis associated with juvenile rheumatoid arthritis two years after the onset of symptoms. The patient had intermittent high fever, rheumatoid rash, polyarthralgia, and hepatosplenomegaly. The joints showed the typical histologic changes of juvenile rheumatoid arthritis. Amyloid deposition was found in various tissues; however, remarkable deposition of amyloid was observed in the gastrointestinal tract, especially in the ileum. The amyloid protein in this patient was identified as protein AA using the methods of potassium permanganate treatment and the peroxidase-antiperoxidase unlabeled antibody technique.     

Major histocompatibility complex class II antigen (HLA-DR, DQ and DP) expression in human fetal skin

Monoclonal antibodies were used to analyse skin samples from human fetuses (15-19 weeks gestational age) for the presence of class II major histocompatibility antigens (HLA-DR, DQ and DP). Cells expressing these antigens were clearly demonstrated within the epidermis from a proportion (4/7) of cases and were completely absent from the others. The negative samples were uniformly those with an epidermis of three cell layers or less. Such material may prove useful in studying the induction of class II antigen expression and the role of these antigens in allostimulation.     

TNF Nco-I RFLP IS NOT AN INDEPENDENT RISK FACTOR IN RHEUMATOID ARTHRITIS

The human TNF genes are located within the MHC class-III region on chromosome 6. The presence or absence of an Nco-I restriction site in the 5’ non-coding sequence of the TNFβ gene defines two alleles (TNFB*1 and TNFB*2). The segregation of these alleles has been associated with levels of TNFα or TNFβ production in systemic lupus erythematosis (SLE), insulin-dependent diabetes mellitus (IDDM) and in healthy control individuals. Rheumatoid arthritis (RA) is characterized by high levels of TNFα within the synovial fluid and to address the question of whether this could be brought about by a genetic predisposition to high TNF production by RA individuals, we examined the distribution of this Nco-I polymorphism in 98 healthy volunteers and 123 patients with active rheumatoid arthritis. No difference was observed between the normal and RA groups with respect to haplotype segregation or allelic frequency. Furthermore, no difference was observed between DR4⁺ or DR4^- individuals in the control or RA groups. These data demonstrate that the high level of TNFα seen in the joints of RA patients is unlikely to be due to a genetic predisposition of these patients to high TNFα production, as defined by the TNF Nco-I restriction fragment length polymorphism (RFLP).     

中国汉人HLA—DQA1基因对类风湿关节炎的遗传易感性研究

用ＰＣＲ－ＰＡＧＥ方法，结合高灵敏的银染色作ＨＬＡ－ＤＱＡ１等位基因分型，研究ＤＱＡ１基因对类风湿关节炎（ＲＡ）的遗传易感性。选择无亲缘关系的广东籍汉族健康者１０６例和５０例ＲＡ患者。发现该方法测的６种ＨＬＡ－ＤＱＡ１等位基因中，ＲＡ组ＤＱＡ１＊０１０１（２７％，ＲＲ＝２．３３４，Ｐ＜０．００５，ＥＦ＝０．１５４）等位基因明显增高；而ＤＱＡ１＊０１０２（１％，ＲＲ＝０．０６８，Ｐ＜０．０１，ＰＦ＝０．５７７）明显下降；ＤＱＡ１的２种纯合子基因型（０１０１／０１０１和０３０１／０３０１）在ＲＡ组明显增高（Ｐ值分别小于０．０２５和０．００５）。上述结果显示：ＨＬＡ－ＤＱＡ１＊０１０１对ＲＡ有遗传易感作用，ＤＱＡ１＊０１０２等位基因有遗传抵抗作用；ＤＱＡ１基因型的检测对预测ＲＡ易感者和判断预后及疗效可能提供理论依据。