Correspondence

Membranous Nephropathy and a TAP1 Gene Polymorphism

N Engl J Med 1994; 331:133-134July 14, 1994

Article

To the Editor:

Membranous glomerulopathy, which is characterized by immune-complex deposits on the epithelial side of the glomerular basement membrane, is one of the most frequent forms of glomerulopathy. The mechanisms responsible for abnormal antibody responses and immune-complex catabolism in this disease are unknown. Nevertheless, an association between membranous nephropathy and the HLA-DR3 class II antigen has been described1. Recently, two “new” genes (TAP1 and TAP2) have been mapped within the HLA class II region2. Each of these genes codes for a transmembrane protein located within the membrane of the endoplasmic reticulum. The noncovalent association of these two proteins constitutes the TAP (transporter associated with antigen processing) dimeric complex. This complex is believed to transport the antigenic peptides from the cytosol to the lumen of the endoplasmic reticulum, in an ATP-dependent manner,3 to allow class I presentation. In HLA class II genes, a polymorphism of these TAP genes has been described,4 which influences antigen presentation in the rat5.

We report on the analysis of TAP1 polymorphism (by the amplification refractory mutation system-polymerase chain reaction) in 70 controls (140 alleles) and 44 patients (88 alleles) with membranous nephropathy. As shown in Table 1Table 1Frequency of TAP1 Alleles in Patients with Membranous Nephropathy and Controls., there was a significant increase in the frequency of the TAP1 B allele in the patients with membranous glomerulopathy (18.2 percent) as compared with that in the controls (7.1 percent) (P<0.02; relative risk, 3.2).

As expected, there was also a significant increase in the frequency of the HLA-DR3 antigen in the patients with membranous nephropathy (45.5 percent), as compared with that in the controls (20 percent) (P<0.01; relative risk, 3.3). To determine whether the increase in the frequency of the TAP1 B allele was related to linkage disequilibrium of this allele with HLA-DR3, we analyzed TAP1 polymorphism in a control group of 49 normal people with HLA-DR3 (98 alleles). The results of this typing did not indicate any linkage disequilibrium between the HLA-DR3 gene and the TAP1 B variant. Hence, there is a clear association between the TAP1 B allele and membranous nephropathy. However, these two risk factors (HLA-DR3 and TAP1 B) were independent and not cumulative. This association suggests the involvement of at least two independent genetic markers possibly involved in the immunologic events leading to membranous nephropathy.

Dominique Chevrier, Sc.D.
Centre Regional de Transfusion Sanguine, 44011 Nantes, France

Magali Giral, M.D.
Centre Hospitalier Regional et Universitaire, 44035 Nantes, France

Veronique Braud, Ph.D.
Centre Regional de Transfusion Sanguine, 44011 Nantes, France

Jean-Paul Soulillou, M.D.
Centre Hospitalier Regional et Universitaire, 44035 Nantes, France

Jean-Denis Bignon, Ph.D.
Centre Regional de Transfusion Sanguine, 44011 Nantes, France

5 References

1. 1

   Klouda PT, Manos J, Acheson EJ, et al. Strong association between idiopathic membranous nephropathy and HLA-DRW3. Lancet 1979;2:770-771
   CrossRef | Web of Science | Medline

2. 2

   Spies T, Bresnahan M, Bahram S, et al. A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway. Nature 1990;348:744-747
   CrossRef | Web of Science | Medline

3. 3

   Neefjes JJ, Momburg F, Hammerling GJ. Selective and ATP-dependent translocation of peptides by the MHC-encoded transporter. Science 1993;261:769-771
   CrossRef | Web of Science | Medline

4. 4

   Colonna M, Bresnahan M, Bahram S, Strominger JL, Spies T. Allelic variants of the human putative peptide transporter involved in antigen processing. Proc Natl Acad Sci U S A 1992;89:3932-3936
   CrossRef | Web of Science | Medline

5. 5

   Powis SJ, Deverson EV, Coadwell WJ, et al. Effect of polymorphism of an MHC-linked transporter on the peptides assembled in a class I molecule. Nature 1992;357:211-215
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   D. Chevrier, M. Giral, R. Perrichot, D. Latinne, P. Coville, J. Y. Muller, J. P. Soulillou, J. D. Bignon. (1997) Idiopathic and secondary membranous nephropathy and polymorphism at TAP1 and HLA-DMA loci. Tissue Antigens 50:2, 164-169
   CrossRef

2. 2

   Peter Kotanko, Charles D. Pusey, Jeremy B. Levy. (1997) RECURRENT GLOMERULONEPHRITIS FOLLOWING RENAL TRANSPLANTATION. Transplantation 63:8, 1045-1052
   CrossRef

3. 3

   Hiroaki Yoshida, Valentina Kon, Iekuni Ichikawa. (1996) Polymorphisms of the renin-angiotensin system genes in progressive renal diseases. Kidney International 50:3, 732-744
   CrossRef