A long-term non-progressor with sickle cell disease and heterozygous mutation for CKR-5 δ-32 chemokine receptor mutation

Duncan Scott, Thomas Harrington

Research output: Contribution to journalArticlepeer-review

Abstract

A 40 year old African American man with Sickle Cell Disease (SS) diagnosed H1V positive in 1990 has been followed in our clinic during the past 10 years. Over this time, he has never manifested any AIDS-defming illnesses and CD4:CD8 ratios and absolute CD4 counts have remained normal. HIV EL1SA and Western Blot studies were positive when repeated and an H1V DNA PCR also confirmed infection. Viral load studies in 1997, 1998, 1999 and 2000 revealed no detectable viral load. Further testing revealed the patient to be heterozygous for the CKR-5 chemokine receptor mutation (δ-32 CKR-5). During the course of this disease the patient never received antiretroviral therapy. Approximately five percent of all HIV-1 infected patients do not progress to AIDS. A variety of theories could account for this phenomenon. The chemokine receptor CKR5 has been shown to be a co-factor for strains of HIV-1 which favor immune system entry via macrophages. A δ-32 CKR-5 chemokine receptor mutation has been found to be present among 10-20% of Caucasians while rare among blacks. A δ-32 CKR-5 chemokine receptor mutation is capable of significantly prolonging the latency period between HIV seropositivity and AIDS because many primary HIV-1 isolates utilize this receptor for entry. Different δ-32 CKR-5 receptor haplotypes which vary among ethnic groups have also been found to be protective against progression of HIV disease. Bagasra et al suggested the association of a slower progression of HIV disease in patients who are homozygous SS. These researchers suggested autosplenectomy, typical of older SS individuals, may be protective since the spleen has a high concentration of CD4+ cells and is a major site of HIV spread once infected. Supporting data for this theory are also offered by Hay and McKernan who reported restoration of CD4+ T lymphocytes in HIV positive individuals who underwent splenectomy for various unrelated reasons such as ITP and trauma. Patients with sickle cell disease suffer life-long anemia and are at risk for lethal infections, however few reports exist characterizing HIV infection in this group. The relative rarity of coexistent SS and AIDS in the medical literature may be due to the slow progression and subclinical H1V infection from unknown mechanisms. Our patient who is an HIV longterm non-progressor represents a rare case of homozygous sickle cell disease with coexisting heterozygous mutation of CKR-5 chemokine receptor (δ-32 CKR-5).

Original languageEnglish (US)
Pages (from-to)37b
JournalBlood
Volume96
Issue number11 PART II
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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