Rheumatology Advance Access originally published online on September 13, 2005
Rheumatology 2005 44(11):1466-1467; doi:10.1093/rheumatology/kei126
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LETTER TO THE EDITOR |
Mixed connective tissue disease: should the diagnosis be more restrictive?: reply
3rd Department of Internal Medicine, University of Debrecen, 4004 Debrecen, Móricz Zs. Str. 22, Hungary
Correspondence to: E. Bodolay, Division of Clinical Immunology, 3rd Department of Internal Medicine, University of Debrecen Medical and Health Science Center, 22 Móricz Street, Debrecen, H-4004, Hungary. E-mail: bodolai{at}iiibel.dote.hu
SIR, Thank you for the comment on our article [1]. The coexistence of several sets of classification criteria for mixed connective tissue disease (MCTD) indicates how difficult it is to give a precise definition of the disease. Recently four sets of criteria have been published, and these are generally used in international publications: the Sharp criteria, the Alarcon-Segovia criteria, the Kasukawa criteria and the Kahn criteria. The basis of these sets criteria is the presence of anti-U1-ribonucleoprotein (RNP) autoantibodies. In fact only the Sharp criteria consider the excluding diagnosis of MCTD in the presence of anti-Sm [2–4]. In 1996 Amiques et al. compared the four sets of criteria to define MCTD. Their results indicated that the classification criteria with the best performance are those proposed by Alarcon-Segovia, with 62.5% sensitivity and 86.2% specificity.
The Alarcon-Segovia criteria are widely used because they contain five clinical symptoms (swollen hands, synovitis, biologically or histologically proven myositis, Raynaud's phenomenon, acrosclerosis with or without proximal systemic sclerosis) and anti-RNP positivity. The presence of the anti-RNP antibody and at least three out of five clinical symptoms are necessary for diagnosis of MCTD. Use of this set of criteria is easy and fast; and for this reason we and some others use this classification. However, MCTD has never has been diagnosed if a patient's serum contains anti-Sm antibodies.
We have followed-up all our patients with MCTD since 1979. A total of 225 patients have fulfilled the diagnostic criteria for MCTD. All patients’ sera contained anti-U1RNP (70 kDa, A and C peptides) antibodies using the U1-RNP-specific antigen enzyme-linked immunosorbent assay test. Over these three decades we have gained more and more knowledge about the pathomechanism and the clinical aspects of MCTD.
Recently it has been discovered that the specific components of the spliceosome complex recognized by MCTD human sera include U1 RNA and the U1-specific polypeptides 70 kDa, A, and C. Hoffman [5] reported that U1 70 kDa reactive T cells have a typical T-helper phenotype and produce cytokines important in B-cell differentiation. They investigated the structure of T-cell receptors on human T-cell clones specific for the U1 70 kDa polypeptide, which were derived from MCTD patients. They found that tested human T-cell clones generated against U1 70 kDa were specific for epitopes within the RNA-binding domain of the protein. Their data suggest that U1-RNP, or a modified form of U1-RNP, may be important in immune targeting and may provoke the autoimmune response.
Long-term studies have shown that more organ damage may develop in MCTD than was first thought in 1972. Oesophageal hypomotility, heart involvement and pulmonary damage, such as interstitial lung disease and pulmonary hypertension, may develop in MCTD. In 1979 an early article on MCTD began ‘MCTD has overlapping clinical features of SLE, SSc, polymyositis and rheumatoid arthritis’. Our opinion is that the clinical manifestations of MCTD mean a symptom complex characteristic of MCTD and these are not overlapping features. Furthermore similar complexes of clinical symptoms are also found in systemic lupus erythematosus and systemic sclerosis.
To summarize: (i) our patients with MCTD were diagnosed only in the presence of anti-U1-RNP excluding the presence of anti-Sm; (ii) the clinical symptoms of MCTD are not the overlapping features of other connective tissue diseases; (iii) an internationally accepted classification of MCTD patients is required.
The authors have declared no conflicts of interest.
References
- Bodolay E, Szekanecz Z, Dévényi K et al. Evaluation of interstitial lung disease in mixed connective tissue disease (MCTD). Rheumatology 2005;44:655–61.
[Free Full Text] - Sharp GC, Irvin WS, Tan EM et al. Mixed connective tissue disease – an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med 1972;52:148–59.[CrossRef][Web of Science][Medline]
- Winn DM, Wolfe JF, Lindberg DA et al. Identification of a clinical subset of systemic lupus erythematosus by antibodies to SM antigen. Arthritis Rheum 1979;22:1334–7.[Web of Science][Medline]
- Amigues JM, Cantagrel A, Abbal M et al. Comparative study of 4 diagnosis criteria sets for mixed connective tissue disease in patients with anti-RNP antibodies. J Rheumatol 1996;23:2055–62.[Web of Science][Medline]
- Hoffman RW, Greidinger EL. Mixed connective tissue disease. Curr Opin Rheumatol 2000;12:386–90.[CrossRef][Web of Science][Medline]
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