Hla type as a predictor of mixed connective tissue disease differentiation ten‐year clinical and immunogenetic followup of 46 patients

Gendi, Nagui; Welsh, Ken I.; Venrooij, Walther J. van; Vancheeswaran, Rama; Gilroy, Jill; Black, Carol M.

doi:10.1002/art.1780380216

Cited by 95 publications

(44 citation statements)

References 46 publications

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“…DRBl"0405, which was associated with arthritis in the present study, is known to be a susceptibility allele for rheumatoid arthritis in the Japanese population (10). Recent analyses by a British group have also shown that the development of rheumatoid arthritis in MCTD patients is associated with DR4 or DRI excluding DRBl"C1103 (11). An association between DQBlh0502 and lupus nephritis was reported in Caucasian patients with SLE (12).…”

Section: Discussionsupporting

confidence: 65%

Clinical correlations with HLA type in Japanese patients with connective tissue disease and anti–U1 small nuclear RNP antibodies

Kuwana

Okano

Kaburaki

et al. 1996

Arthritis & Rheumatism

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Objective. To elucidate the roles of HLA genes in the clinical presentation of patients with connective tissue disease and serum anti-U1 small nuclear RNP antibody.Methods. HLA class I antigens and HLA class I1 alleles were determined in 43 Japanese patients with anti-U1 RNP antibody alone, by microcytotoxicity testing and DNA typing, respectively. Prospectively recorded clinical and laboratory features were analyzed in relation to HLA class I and class I1 types.Results. DQB1*0303 was associated with lupusrelated symptoms including fever, malar rash, oral ulcers, hypocomplementemia, and high-titer antidouble-stranded DNA antibody. Other HLA-clinical associations included DR2 with pleuritis, DR4 with hand swelling, and DRB1*0405 with arthritis.Conclusion. These HLA-clinical associations explain, in part, the heterogeneous clinical presentation in patients with anti-U1 RNP antibody.Autoantibody to U1 small nuclear RNP is a dominant feature of the autoimmune response that occurs in patients with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD) (1). However, the clinical presentation of patients with anti-U1 RNP antibody is variable; for example, some patients have SLE alone, but others have overlapping symptoms of systemic sclerosis (SSc) and myositis (1).Supported by the Scleroderma Grant for Intractable Disease from the Japanese Ministry of Health and Welfare, and grants-in-aid from the Ministry of Education, Science, and Culture, Japan.Masataka Kuwana, MD, Junichi Kaburaki, MD: Keio University School of Medicine, Tokyo, Japan; Yutaka Okano, MD: Nippon Kokan Hospital, Kawasaki, Japan; Hidetoshi Inoko, PhD: Tokai University School of Medicine, Isehara, Japan.Address reprint requests to Masataka Kuwana, MD, Division of Rheumatology, Department of Medicine, Keio University School of Medicine, 35 Shinano-machi; Shinjuku-ku, Tokyo 160, Japan.Submitted for publication November 20, 1995; accepted in revised form January 30, 1996. Despite efforts to explain this clinical heterogeneity in patients with anti-U1 RNP antibody based on immunoreactivities against individual U1 RNP constituent proteins (70K, A, B/B', and C ) or immunoglobulin allotypes, no strong and reproducible clinical associations with these markers have been reported except in the case of anti-70K reactivity, which is associated with Raynaud's phenomenon, sclerodactyly, hand swelling, telangiectasias, and abnormal esophageal motility (2).Recent molecular analyses of HLA class I1 genes have revealed associations between various antinuclear antibodies and polymorphisms of HLA (3). We have reported that immunoreactivities against individual U1 RNP constituent proteins as well as antibody titer were associated with several shared epitopes located on HLA-DR and D Q genes (4). In the present study, we sought HLA-clinical associations in Japanese patients with connective tissue disease and anti-U1 RNP antibody, to better define the role of HLA genes in the clinical presentation. PATIENTS AND METHODSPatients. Forty-three unrelated Ja...

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Section: Discussionsupporting

confidence: 65%

Clinical correlations with HLA type in Japanese patients with connective tissue disease and anti–U1 small nuclear RNP antibodies

Kuwana

Okano

Kaburaki

et al. 1996

Arthritis & Rheumatism

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“…For example, a polymorphism in the promoter of the tumour necrosis factor-α gene is increased in dermatomyositis/polymyositis patients with ILD (OR 2.1, 95% CI 1.0-4.3) [71]. The HLA-DRB1*03 haplotype, a determinant factor in the development of ILD among patients with CTDs [72,73], predicts a higher risk of ILD in dermatomyositis/polymyositis [74], irrespective of the myositis subtype or the presence of autoantibodies [56]. Anti-PM/Scl and anti-ARS antibodies also share the same prevalence of HLA-DRB1*03, DQA1*05 and DQB1*02 haplotypes [75,76].…”

Section: Pathogenesismentioning

confidence: 99%

Idiopathic inflammatory myopathies and the lung

et al. 2015

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Idiopathic inflammatory myositis (IIM) is a group of rare connective tissue diseases (CTDs) characterised by muscular and extramuscular signs, in which lung involvement is a challenging issue. Interstitial lung disease (ILD) is the hallmark of pulmonary involvement in IIM, and causes morbidity and mortality, resulting in an estimated excess mortality of 50% in some series. Except for inclusion body myositis, these extrapulmonary disorders are associated with the general and visceral involvement frequently found in other CTDs including fever, Raynaud's phenomenon, arthralgia, nonspecific cutaneous modifications and ILD, for which the prevalence is estimated to be up to 65%. Substantial heterogeneity exists within the spectrum of IIMs, and each condition is associated with various frequencies and subtypes of pulmonary involvement. This heterogeneity is partly related to the presence of various autoantibodies encompassing anti-synthetase, anti-MDA5 and anti-PM/Scl. ILD is present in all subsets of IIM including juvenile myositis, but is more frequent in dermatomyositis and overlap myositis. IIM can also be associated with other presentations of respiratory involvement, namely pulmonary arterial hypertension, pleural disease, infections, drug-induced toxicity, malignancy and respiratory muscle weakness. Here, we critically review the current knowledge about adult and juvenile myositis-associated lung disease with a detailed description of therapeutics for chronic and rapidly progressive ILD. @ERSpublications Interstitial lung disease is a leading cause of morbidity in dermatomyositis/polymyositis

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“…Associations between certain HLAtypes and MCTDhave been reported by several investigators (3). Gendi et al ( 13) demonstrated that non-differentiated MCTD is associated with HLA-DR2or DR4. This genetic factor (HLA-DR2)maycontribute to the occurrence of MCTD in the present patient.…”

Section: Discussionmentioning

confidence: 99%

Mixed Connective Tissue Disease Associated with von Recklinghausen's Nurofibromatosis.

Migita¹,

Kawabe

Mori³

et al. 2001

Intern. Med.

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Wereport a 42-year-old Japanese womanwith Recklinghausen's neurofibromatosis 1 (NF1) who developed mixed connective tissue disease (MCTD). Previously experiencing good health without an increase in subcutaneous nodules, she presented with Raynaud's phenomenon, swollen hands and polyarthralgia. Clinical examination revealed a high titer of anti-RNP antibody, and she was thus diagnosed as having MCTD. She was treated with oral prednisolone (10 mg/day) and her symptoms improved rapidly.Since the association of MCTD and NF1 has not been reported previously, we concluded that this association is rare. Wealso discussed the association of NF1and autoimmune diseases including MCTD.

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Hla type as a predictor of mixed connective tissue disease differentiation ten‐year clinical and immunogenetic followup of 46 patients

Cited by 95 publications

References 46 publications

Clinical correlations with HLA type in Japanese patients with connective tissue disease and anti–U1 small nuclear RNP antibodies

Clinical correlations with HLA type in Japanese patients with connective tissue disease and anti–U1 small nuclear RNP antibodies

Idiopathic inflammatory myopathies and the lung

Mixed Connective Tissue Disease Associated with von Recklinghausen's Nurofibromatosis.

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