Correspondence
Fetal DNA and Cells in Women with Systemic Sclerosis
N Engl J Med 1998; 339:771-772September 10, 1998
- Article
To the Editor:
Artlett et al. (April 23 issue)1 put forward the provocative hypothesis that systemic sclerosis may be caused by a graft-versus-host–like reaction induced by retained fetal cells in the mother. Although the hypothesis is intriguing, the occurrence of systemic sclerosis in men and nulliparous women clearly indicates that antimaternal reactions are not the sole basis of the disease. Furthermore, we believe that the similarities between graft-versus-host disease and systemic sclerosis are outweighed by considerable differences that make the two entities readily distinguishable.
Fibrosis occurs in only a minority of patients with graft-versus-host disease, develops late in the course of the disease, and is characterized by a central distribution, whereas fibrosis occurs in most patients with systemic sclerosis, develops early in the course of the disease, and is characterized by an acral distribution. Liver involvement is common in graft-versus-host disease but rare in systemic sclerosis. Raynaud's phenomenon is unusual in patients with graft-versus-host disease but occurs in a majority of patients with systemic sclerosis. Histopathologically, graft-versus-host disease is characterized by fibrotic changes concentrated in the papillary (superficial) dermis, whereas systemic sclerosis is characterized by a sclerotic pattern throughout the reticular dermis, most prominently in the deep reticular dermis at the level of subcutaneous fat. Finally, graft-versus-host disease responds to several immunosuppressive drugs,2 whereas systemic sclerosis does not.3 Thus, the dissimilar clinical and pathological features of graft-versus-host disease and systemic sclerosis raise questions about the use of graft-versus-host disease as a model for systemic sclerosis.
3 ReferencesM. Kari Connolly, M.D.
Timothy H. McCalmont, M.D.
University of California, San Francisco, San Francisco, CA 94143-05171
Artlett CM ,Smith JB ,Jimenez SA . Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis. N Engl J Med 1998;338:1186-1191
Full Text | Web of Science | Medline2
Sullivan KM ,Witherspoon RP ,Storb R , et al. Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease. Blood 1988;72:555-561
Web of Science | Medline3
Pope JE . Treatment of systemic sclerosis. Rheum Dis Clin North Am 1996;22:893-907
CrossRef | Web of Science | Medline
To the Editor:
Artlett et al. have clearly demonstrated the presence of increased numbers of cells with a male chromosomal pattern in skin lesions and peripheral blood from women with a recent onset of systemic sclerosis. In their discussion, however, the authors do not consider the possibility that the persistence of fetal cells in tissues from women with this disease may reflect ineffective destruction of fetal cells entering the women's circulation during pregnancy due to compromised immunologic function, instead of representing the stimulus for the development of sclerotic changes. An underlying immunologic abnormality would explain not only the persistence of fetal cells in women with systemic sclerosis but also the occurrence of the disease in men and nulliparous women.
Harry W. Daniell, M.D.
2626 Edith Ave., Redding, CA 96001Author/Editor Response
The authors reply:
To the Editor: We agree with Drs. Connolly and McCalmont that the hypothesis that systemic sclerosis may be caused by a graft-versus-host–like reaction induced by retained fetal cells in the mother would not explain the pathogenesis of systemic sclerosis in all patients. We suggested that the passage of maternal cells across the placenta to the fetus during pregnancy or the retention of cells from prior blood transfusions may be an alternative mechanism for the acquisition of foreign cells. We also agree that there are substantial clinical and histopathological differences between systemic sclerosis and graft-versus-host disease, but they are similar in that tissue fibrosis and certain immunologic abnormalities in host tissues can be induced by chimeric cells from a graft. If fetal cells retained in the maternal circulation and tissues can initiate an attack on maternal tissues that leads to systemic sclerosis, as suggested by the hypothesis, the resultant clinical manifestations may well be different from those of graft-versus-host disease. Numerous factors could explain such differences, including the genetic susceptibility to systemic sclerosis, the effects of immunosuppressive drugs given to patients receiving organ transplants, and the possible contribution of environmental exposure to the pathogenesis of systemic sclerosis.
In response to the comments of Dr. Daniell, we believe that there are no conclusive clinical or laboratory data to support the concept that patients with systemic sclerosis are chronically immunosuppressed, unless they have received treatment with glucocorticoids or other immunosuppressive drugs.
Carol M. Artlett, Ph.D.
J. Bruce Smith, M.D.
Sergio A. Jimenez, M.D.
Thomas Jefferson University, Philadelphia, PA 19107-5541- Citing Articles (3)
Citing Articles
1
Levi Fried, Robert S. Kirsner, Sulochana Bhandarkar, Jack L. Arbiser. (2008) Efficacy of Rapamycin in Scleroderma: A Case Study. Lymphatic Research and Biology 6:3-4, 217-219
CrossRef2
DANIEL F. JIMENEZ AND, ALICE F. TARANTAL. (2003) Quantitative Analysis of Male Fetal DNA in Maternal Serum of Gravid Rhesus Monkeys (Macaca mulatta). Pediatric Research 53:1, 18-23
CrossRef3
Monique Gannag
, Zahir Amoura, Olivier Lantz, Jean-Charles Piette, Sophie Caillat-Zucman. (2002) Feto-maternal microchimerism in connective tissue diseases. European Journal of Immunology 32:12, 3405-3413
CrossRef
