Rheumatology Advance Access originally published online on September 13, 2005
Rheumatology 2005 44(11):1465-1466; doi:10.1093/rheumatology/kei125
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LETTER TO THE EDITOR |
Mixed connective tissue disease: should the diagnosis be more restrictive? Comment on the article by Bodolay et al.
Internal Medicine Dept, Vall d'Hebron General Hospital and 1 Statistical Dept, Universitat Politécnica Barcelona, Barcelona, Spain.
Correspondence to: A. Selva-O'Callaghan, C/Siracusa no 12 bis ‘A’, Barcelona-08012, Spain E-mail: aselva{at}vhebron.net
SIR, We read with great interest the original contribution of Bodolay et al. [1], and we would like to comment on some issues in regard to this study. Mixed connective tissue disease (MCTD) was originally described by Sharp et al. [2] in 1972 in patients with a combination of features found in different connective tissue diseases and a characteristic serological marker, the presence of antibodies against U1 small nuclear ribonucleoprotein (RNP) autoantigen. The existence of MCTD as a distinct disease entity has been a matter of controversy among rheumatologists since it was first described. Specific diagnostic criteria allow us to classify and to separate MCTD from other autoimmune systemic diseases. Three different sets of criteria have been proposed by Sharp, Alarcon-Segovia and Kasukawa, but correlation among them is not optimal. Bodolay et al. [1] in their study utilized the Alarcon-Segovia criteria which do not take into account the positivity to Sm antigen as an exclusion criterion. It is known that both the U1-RNP and Sm antigens are components of the spliceosome complex, whose function is to assist in splicing pre-messenger RNA to mature RNA, and that systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) also express autoantibodies to several protein components of spliceosome [3]. So it is probable that with more restrictive criteria, specifically taking into account the Sm antigen, some of the patients categorized in their study as MCTD will not be so classified. Smolen and Steiner [4] have shown in a cross-sectional study that 92% of patients who satisfied the Alarcon-Segovia criteria could also be classified as having MCTD according to the Kasuwaka criteria, but only 70% according to the Sharp criteria. We recently carried out a similar study in Barcelona; from a large series of patients with autoimmune systemic diseases treated at our out-patient clinic, we initially selected patients with positivity to anti-RNP antibodies by enzyme-linked immunosorbent assay (Inno-Lia ANA UpDate kit; Innogenetics, Ghent, Belgium). Fifty-one patients were identified with positivity to anti-RNP antibodies, and 21 of these were rejected because of the presence of Sm antibodies which are considered to be specific to SLE. Ribonucleic acid immunoprecipitation from HeLa S3 cell extracts was performed in the 30 remaining patients to confirm the presence of anti-U1-RNP antibodies, and only 22 patients out of 30 (75%) were positive. In order to study the presence of anti-RNP by enzyme-linked immunosorbent assay and RNA immunoprecipitation, serum samples were obtained at the same time to avoid the effect of epitope contraction that has been described in patients with MCTD [5]. Among patients who satisfied the Alarcon-Segovia criteria, a specific positive and negative accord with the Kasuwaka criteria was obtained in 79 and 40%, respectively, and in 75 and 50% with the Sharp criteria. When different sets of diagnostic criteria were applied, a tetrachoric correlation was statistically significant only between the Sharp and the Kasuwaka criteria (P = 0.044; r = 0.426), so the agreement among the different sets of criteria is only partial. Taking all these data together, it is our opinion that in order to better study and improve our knowledge of MCTD, the most restrictive criteria—clinical and immunological—should be used. The Sharp criteria which specifically exclude patients with anti-Sm antibodies and confirmation of anti-U1-RNP by RNA immunoprecipitation are recommended where possible.
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, Gould RG, Holman RH. 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]
- Ruiz-Pombo M, Labrador-Horrillo M, Selva-O'Callaghan A. Undifferentiated, overlapping and mixed connective tissue diseases. Med Clin (Barc). 2004;123:712–17.[Medline]
- Smolen JF, Steiner G. Mixed connective tissue disease. To be or not to be? Arthritis Rheum 1998;41:768–77.[CrossRef][Web of Science][Medline]
- Hoffman RW, Greidinger EL. Mixed connective tissue disease. Curr Opin Rheumatol 2000;12:386–90.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||