Circulating loxl2 levels reflect severity of intestinal fibrosis and galt cd4+ t lymphocyte depletion in treated hiv infection

Sophie Seang, Anoma Somasunderam, Maitreyee Nigalye, Ma Somsouk, Timoty W. Schacker, Joyce L. Sanchez, Peter W. Hunt, Netanya S. Utay, Jordan E. Lake

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Incomplete immune reconstitution may occur despite successful antiretroviral therapy (ART). Gut-associated lymphoid tissue (GALT) fibrosis may contribute via local CD4+ T lymphocyte depletion, intestinal barrier disruption, microbial translocation, and immune activation. Methods: In a cross-sectional analysis, we measured circulating fibrosis biomarker levels on cryopreserved plasma from adult HIV-infected (HIV+) SCOPE study participants on suppressive ART who also had fibrosis quantification on recto-sigmoid biopsies. Relationships among biomarker levels, clinical and demographic variables, GALT lymphoid aggregate (LA) collagen deposition, and LA CD4+ T lymphocyte density were analyzed using simple regression. Biomarker levels were also compared to levels in HIV+ viremic SCOPE participants and a convenience sample of HIV-uninfected (HIV-) samples. Results: HIV+ aviremic participants (n = 39) were 92% male and 41% non-white, with median age 48 years, CD4+ T lymphocyte count 277 cells/mm3, and 17 years since HIV diagnosis. Most biomarkers were lower in HIV− (n = 36) vs HIV+ aviremic individuals, although CXCL4 levels were higher. HIV+ viremic individuals (N = 18) had higher median TGF-ß3, CIC-C1Q, and TIMP-1 (P < 0.05) and lower LOXL2 levels (P = 0.08) than HIV+ aviremic individuals. Only higher LOXL2 levels correlated with more GALT collagen deposition (R = 0.44, P = 0.008) and lower LA CD4+ T lymphocyte density (R = −0.32, P = 0.05) among aviremic individuals. Conclusions: Circulating LOXL2 levels may be a noninvasive measure of intestinal fibrosis and GALT CD4+ T lymphocyte depletion in treated HIV infection. LOXL2 crosslinks elastin and collagen, and elevated LOXL2 levels occur in pathologic states, making LOXL2 inhibition a potential interventional target for intestinal fibrosis and its sequelae.

Original languageEnglish (US)
Pages (from-to)239-252
Number of pages14
JournalPathogens and Immunity
Volume2
Issue number2
DOIs
StatePublished - 2017

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grants K23 AI110532 to JEL and 5P30 AI028697. The SCOPE cohort was supported the UCSF/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763), the UCSF Clinical and Translational Research Institute Clinical Research Center (UL1 RR024131), and the CFAR Network of Integrated Systems (R24 AI067039). Additional support was provided by the Delaney AIDS Research Enterprise (DARE; AI096109) and the amfAR Institute for HIV Cure Research (amfAR 109301).

Funding Information:
This work was supported by National Institutes of Health Grants K23 AI110532 to JEL and 5P30 AI028697. The SCOPE cohort was supported the UCSF/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763), the UCSF Clinical and Translational Research Institute Clinical Research Center (UL1 RR024131), and the CFAR Network of Integrated Systems (R24 AI067039). Additional support was provided by the Delaney AIDS Research Enterprise (DARE; AI096109) and the amfAR Institute for HIV Cure Research (amfAR 109301). We would like to acknowledge Dr. Benigno Rodriguez for his kind donation of HIV-uninfected plasma samples.

Publisher Copyright:
© Pathogens and Immunity 2017.

Keywords

  • Fibrosis
  • GALT
  • HIV
  • Immune reconstitution

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