Genetic deficiency of complement isoforms C4A or C4B predicts improved survival of metastatic renal cell carcinoma.

The Journal of Urology
Ghazal I ZafarJulie A Ellerhorst

Abstract

Autoimmune phenomena during immunotherapy are associated with favorable outcomes in patients with metastatic renal cell carcinoma. We have reported improved survival in patients with stage IV renal cell carcinoma who carry autoimmunity associated HLA class II haplotypes. We propose that the clinical benefit is mediated by products of other autoimmunity associated genes linked to these haplotypes. A candidate gene is complement C4, which replicates as part of the RCCX module, can be present in multiple copies and exists as C4A and C4B isoforms. Deficiencies of either isoform are associated with autoimmunity. In the current study we tested the hypothesis that C4A or C4B deficiency predicts improved survival of patients with RCC. The total C4 copy number was determined by simultaneous amplification of RP1 and TNXA/RP2 to quantitate RCCX modules. C4A and C4B alleles were distinguished by PshAI restriction fragment length polymorphism. Genetic complotypes were determined in 61 patients. Individuals with a solitary copy of either C4 isoform experienced longer survival. Median survival from the diagnosis of metastatic disease in patients with a solitary copy of C4A or C4B was 7.75 years vs 1.25 in the comparison group (p = 0.001). Thi...Continue Reading

References

Dec 10, 1998·Immunity·A P ProdeusM C Carroll
Jan 23, 1999·The Journal of Urology·R A Figlin
Mar 11, 1999·Experimental and Clinical Immunogenetics·G MauffJ M Moulds
Mar 18, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·A FranzkeJ Atzpodien
Jan 15, 2004·Current Directions in Autoimmunity·Yan YangC Yung Yu
Oct 2, 2004·Nature Reviews. Immunology·Michael C Carroll
Feb 17, 2006·The New England Journal of Medicine·Helen GogasJohn M Kirkwood
Aug 23, 2006·Autoimmunity·M J Lewis, M Botto
Oct 9, 2007·Journal of Clinical Rheumatology : Practical Reports on Rheumatic & Musculoskeletal Diseases·Brooke E GilliamTerry L Moore

❮ Previous
Next ❯

Citations

Aug 24, 2010·International Journal of Urology : Official Journal of the Japanese Urological Association·Seiichi OrikasaIzuru Minemura
Jul 3, 2018·British Journal of Cancer·Anna TuhkuriSuvi Renkonen
Jul 19, 2017·International Journal of Legal Medicine·Noha El-KashefMartin Juebner

❮ Previous
Next ❯

Related Concepts

Related Feeds

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.