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Year : 2005  |  Volume : 51  |  Issue : 2  |  Page : 108

Delayed development of pulmonary hypertension in mixed connective tissue disease

University of Miami Miller School of Medicine and VAMC, 1400 NW 10th Avenue, Suite 602, Miami, FL 33136, USA

Correspondence Address:
Eric L Greidinger
University of Miami Miller School of Medicine and VAMC, 1400 NW 10th Avenue, Suite 602, Miami, FL 33136
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Source of Support: None, Conflict of Interest: None

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How to cite this article:
Greidinger EL. Delayed development of pulmonary hypertension in mixed connective tissue disease. J Postgrad Med 2005;51:108

How to cite this URL:
Greidinger EL. Delayed development of pulmonary hypertension in mixed connective tissue disease. J Postgrad Med [serial online] 2005 [cited 2023 Jun 6];51:108. Available from:

The paper, "Pulmonary hypertension not a major feature of early mixed connective tissue disease: A prospective clinicoserological study" published in this issue describes the clinical manifestations of 13 recently diagnosed patients who satisfy standard classification criteria for Mixed Connective Tissue Disease (MCTD), from a cohort of 1500 patients seen at a rheumatology referral centre in India between 2002 and 2004.[1] Consistent with prior reports that go on to find that it is ultimately the leading cause of death from MCTD,[2] the authors find that pulmonary hypertension is seldom present early in the course of MCTD.

Since the immune response in MCTD has been found to evolve over time,[3] one potential explanation for the late and inconsistent development of pulmonary hypertension in MCTD is that anti-lung autoimmunity emerges late in the course of the disease. Reactivity between some RNP autoantibodies (and other MCTD-associated autoantibodies) and the respiratory tract has been observed.[4] T cell infiltrates are also seen at sites of MCTD end organ injury including the lung.[5] The specificities and evolution of any such anti-lung-specific response in MCTD remain to be further defined, however.

The recent development of an animal model of MCTD-like perivascular and interstitial lung disease after immunization with an RNP peptide may lead to further insights.[6] In the mouse model, as has been reported in humans,[7] perivascular pulmonary inflammatory infiltrates can be observed frequently, even in the absence of clinical evidence of pulmonary hypertension, and even at time points early in the disease. Thus, although a lag exists between the clinical expression of pHTN and other MCTD manifestations, this may be attributable to the extent of lung injury that must occur before pHTN becomes clinically apparent, as opposed to possible delays in the development of an anti-lung-specific component of the MCTD immune response.

As their number and duration of follow-up grows, it will be of relevance to continue to compare the manifestations, pulmonary and otherwise, seen in this cohort of Indian MCTD patients to those reported in other ethnic groups. Thus far, it is remarkable that across multiple ethnic groups and multiple investigators, the prevalence of individual clinical manifestations in MCTD seems generally similar (at least given the wide confidence intervals that small sample sizes bring). This suggests that MCTD seen around the world is likely to be linked by common pathophysiology. If pHTN remains less common in Indian patients than has been reported in Caucasian and Japanese cohorts over time,[2],[7] immunologic and genetic studies of this group may help elucidate the factors leading to pHTN in MCTD. Thus, findings from this new cohort in India are likely to continue to be of interest to the worldwide MCTD community.

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1.Haroon N, Nisha RS, Chandran V, Bharadwaj A. Pulmonary hypertension not a major feature of early mixed connective tissue disease: A prospective clinicoserological study. J Postgrad Med 2005;51:104-8.  Back to cited text no. 1    
2.Burdt MA, Hoffman RW, Deutscher SL, Wang GS, Johnson JC, Sharp GC. Long-term outcome in mixed connective tissue disease: longitudinal clinical and serologic findings. Arthritis Rheum 1999;42:899-909.  Back to cited text no. 2  [PUBMED]  
3.Greidinger EL, Hoffman RW. The appearance of U1 RNP antibody specificities in sequential autoimmune human antisera follows a characteristic order that implicates the U1-70 kd and B'/B proteins as predominant U1 RNP immunogens. Arthritis Rheum 2001;44:368-75.  Back to cited text no. 3  [PUBMED]  
4.Okawa-Takatsuji M, Aotsuka S, Uwatoko S, Kinoshita M, Sumiya M. Increase of cytokine production by pulmonary artery endothelial cells induced by supernatants from monocytes stimulated with autoantibodies against U1-ribonucleoprotein. Clin Exp Rheumatol 1999;17:705-12.  Back to cited text no. 4  [PUBMED]  
5.Suzuki E, Tsukada H, Ishida T, Ishizuka O, Hasegawa T, Gejyo F. Correlation between the numbers of gammadelta T cells and CD4+ HLA-DR+ T cells in broncho-alveolar lavage fluid from patients with diffuse lung disease. Tohoku J Exp Med 2002;196:231-40.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Greidinger EL, Foecking MF, Magee J, Wilson L, Ranatunga S, Ortmann RA, Hoffman RW. A major B cell epitope present on the apoptotic but not the intact form of the U1-70-kDa ribonucleoprotein autoantigen. J Immunol 2004;172:709-16.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Sasaki N, Kurose A, Inoue H, Sawai T. A possible role of anti-endothelial cell antibody in the sera of MCTD patients on pulmonary vascular damage relating to pulmonary hypertension. Ryumachi 2002;42:885-94.  Back to cited text no. 7  [PUBMED]  

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Online since 12th February '04
2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
Published by Wolters Kluwer - Medknow