Correspondence

Systemic Lupus Erythematosus

N Engl J Med 1994; 331:1235November 3, 1994

Article

To the Editor:

We believe that some important aspects of the immunogenetics and the pathogenesis of systemic lupus erythematosus (SLE) are missing in the review article by Mills on SLE (June 30 issue).1 Mills states that many clinical manifestations of SLE are the consequence of tissue damage from vasculopathy mediated by immune complexes. In this context he should mention the important link between complement deficiencies and SLE. The strongest disease-susceptibility genes to be identified in humans are those encoding deficiencies of proteins of the classic pathway of complement, especially C1q, C2, and C4.2,3 Over 75 percent of patients with a deficiency of C1q, C1r, C1s, or C4 have the disease. Although these patients make up only a very small percentage of patients with SLE, they serve to emphasize the importance of altered immune-complex processing in the pathogenesis of SLE.

In addition, a partial inherited deficiency of C4 increases susceptibility to the disease.4 A number of studies found an increased prevalence of C4A null alleles in white patients with SLE. There is strong linkage disequilibrium between C4AQ0 alleles and the HLA-B8/DR3 haplotype in whites. HLA-DR2 and DR3 alleles are independently associated with SLE. In Japanese populations, however, where HLA-DR3 is very rare, the association between the HLA haplotypes and SLE breaks down and the association of SLE with C4AQ0 alleles is sustained.5

Thomas Hohler, M.D., M.Sc.
Karl-Heinz Meyer zum Buschenfelde, M.D., Ph.D.
Johannes Gutenberg-Universitat Mainz Klinikum, 38121 Mainz, Germany

5 References

1. 1

   Mills JA. Systemic lupus erythematosus. N Engl J Med 1994;330:1871-1879
   Full Text | Web of Science | Medline

2. 2

   Loos M, Heinz HP. Component deficiencies. 1. The first component: C1q, C1r, C1s. Prog Allergy 1986;39:212-231
   Medline

3. 3

   Hauptmann G, Goetz J, Uring-Lambert B, Grosshans E. Component deficiencies. 2. The fourth component. Prog Allergy 1986;39:232-249
   Medline

4. 4

   Fielder AH, Walport MJ, Batchelor JR, et al. Family study of the major histocompatibility complex in patients with systemic lupus erythematosus: importance of null alleles of C4A and C4B in determining disease susceptibility. BMJ 1983;286:425-428
   CrossRef | Web of Science | Medline

5. 5

   Dunckley H, Gatenby PA, Hawkins B, Naito S, Serjeantson SW. Deficiency of C4A is a genetic determinant of systemic lupus erythematosus in three ethnic groups. J Immunogenet 1987;14:209-218
   CrossRef | Medline

To the Editor:

In reading Dr. Mills's review article on SLE, I was baffled to read that “the concordance rate in monozygotic twins is between 30 and 50 percent,” particularly since my colleagues and I wrote the article cited.1 Our finding, from the largest published study of SLE in twins, was that just 24 percent of monozygotic pairs of twins were concordant.

Dennis Deapen, Dr.P.H.
University of Southern California School of Medicine, Los Angeles, CA 90033-1042

1 References

1. 1

   Deapen D, Escalante A, Weinrib L, et al. A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis Rheum 1992;35:311-318
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Mills replies:

To the Editor: I thank Drs. Hohler and Meyer zum Buschenfelde for pointing out that a lupus-like illness develops in a majority of children with deficiencies of an early complement component. Although the postulated mechanism is the failure to clear immune complexes normally, the case has not been proved. An abnormal response to infection is also a possibility, as are other less well defined roles for complement.

The lupus syndrome in children who have a deficiency of complement is atypical. Dermatologic manifestations are prominent, but there is relatively little immune-complex deposition at the dermoepidermal junction, contrary to what would be expected if the failure to clear immune complex was the responsible mechanism.1

The brief section of the review concerning pathogenesis left out a number of interesting topics. For more extensive, up-to-date information about clinical and pathogenic aspects of SLE, readers are directed to a recent series edited by William McCune.2

I stand corrected by Dr. Deapen. He and his collaborators found that only 25 percent of 44 pairs of identical female twins were concordant for SLE. Since there is likely to be a reporting bias in favor of concordant twins, the true rate may be even lower. Smaller series that are more likely to have been influenced by reporting bias have shown a concordance rate for SLE in identical twins as high as 59 percent. Only one set of monozygotic male twins was located, so the concordance rate in male twins is uncertain.

John A. Mills, M.D.
Massachusetts General Hospital, Boston, MA 02114

2 References

1. 1

   Arnett FC, Reveille JD. Genetics of systemic lupus erythematosus. Rheum Dis Clin North Am 1992;18:865-892
   Web of Science | Medline

2. 2

   Systemic lupus erythematosusRheum Dis Clin North Am 1994;20:1-308
   Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   J. F. Viallard, C. Bloch-Michel, M. Neau-Cransac, J. L. Taupin, S. Garrigue, V. Miossec, P. Mercie, J. L. Pellegrin, J. F. Moreau. (2001) HLA-DR expression on lymphocyte subsets as a marker of disease activity in patients with systemic lupus erythematosus. Clinical and Experimental Immunology 125:3, 485-491
   CrossRef