HLA-B*57 versus HLA-B*81 in HIV-1 infection: slow and steady wins the race?

Two human leukocyte antigen (HLA) variants, HLA-B*57 and -B*81, are consistently known as favorable host factors in human immunodeficiency virus type 1 (HIV-1)-infected Africans and African-Americans. In our analyses of prospective data from 538 recent HIV-1 seroconverters and cross-sectional data from 292 subjects with unknown duration of infection, HLA-B*57 (mostly B*57:03) and -B*81 (exclusively B*81:01) had mostly discordant associations with virologic and immunologic manifestations before antiretroviral therapy. Specifically, relatively low viral load (VL) in HLA-B*57-positive subjects (P ≤ 0.03 in various models) did not translate to early advantage in CD4(+) T-cell (CD4) counts (P ≥ 0.37). In contrast, individuals with HLA-B*81 showed little deviation from the normal set point VL (P > 0.18) while maintaining high CD4 count during early and chronic infection (P = 0.01). These observations suggest that discordance between VL and CD4 count can occur in the presence of certain HLA alleles and that effective control of HIV-1 viremia is not always a prerequisite for favorable prognosis (delayed immunodeficiency). Of note, steady CD4 count associated with HLA-B*81 in HIV-1-infected Africans may depend on the country of origin, as observations differed slightly between subgroups enrolled in southern Africa (Zambia) and eastern Africa (Kenya, Rwanda, and Uganda).

Increased plasma interleukin 6 concentrations and exaggerated adipose tissue interleukin 6 content in severely obese patients after operative trauma.

BACKGROUND: The cytokine response to operative trauma may be altered in obesity. Thus, we monitored changes in systemic and adipose tissue content of interleukin 6 (IL-6) and in insulin resistance in nonobese versus severely obese patients before and immediately after abdominal operations. METHODS: At the beginning and the end of operation, blood samples and biopsies consisting of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were collected from 13 nonobese and 33 severely obese patients. Systemic concentrations of glucose, insulin, and IL-6, as well as adipose tissue content of IL-6, were determined. RESULTS: Plasma IL-6 concentration and adipose tissue content of IL-6 increased, compared with baseline in patients after operation (plasma, 13- and 5.7-fold; VAT, 270- and 210-fold; SAT, 79- and 8.2-fold in severely obese vs nonobese patients, respectively). The increase in IL-6 in plasma and in both VAT and SAT was exaggerated in severely obese patients, compared with nonobese patients. Increases after operation in plasma IL-6 concentrations were correlated positively to the corresponding increases in both SAT and VAT IL-6 content (r = 0.57 and 0.66, respectively). Also, we found a positive correlation between the worsening of insulin resistance and increases in both plasma and SAT IL-6 concentrations (r = 0.40 and 0.51, respectively). CONCLUSIONS: Circulating IL-6 concentrations both at baseline and after operation are related strongly to abdominal adipose tissue content of content of IL-6 and are exaggerated in severely obese persons. After operation, worsening of insulin resistance is associated with increasing plasma and adipose tissue content of IL-6.

Human leukocyte antigens and HIV type 1 viral load in early and chronic infection: predominance of evolving relationships.

BACKGROUND: During untreated, chronic HIV-1 infection, plasma viral load (VL) is a relatively stable quantitative trait that has clinical and epidemiological implications. Immunogenetic research has established various human genetic factors, especially human leukocyte antigen (HLA) variants, as independent determinants of VL set-point. METHODOLOGY/PRINCIPAL FINDINGS: To identify and clarify HLA alleles that are associated with either transient or durable immune control of HIV-1 infection, we evaluated the relationships of HLA class I and class II alleles with VL among 563 seroprevalent Zambians (SPs) who were seropositive at enrollment and 221 seroconverters (SCs) who became seropositive during quarterly follow-up visits. After statistical adjustments for non-genetic factors (sex and age), two unfavorable alleles (A*3601 and DRB1*0102) were independently associated with high VL in SPs (p<0.01) but not in SCs. In contrast, favorable HLA variants, mainly A*74, B*13, B*57 (or Cw*18), and one HLA-A and HLA-C combination (A*30+Cw*03), dominated in SCs; their independent associations with low VL were reflected in regression beta estimates that ranged from -0.47+/-0.23 to -0.92+/-0.32 log(10) in SCs (p<0.05). Except for Cw*18, all favorable variants had diminishing or vanishing association with VL in SPs (p