TY - JOUR
T1 - Circulating loxl2 levels reflect severity of intestinal fibrosis and galt cd4+ t lymphocyte depletion in treated hiv infection
AU - Seang, Sophie
AU - Somasunderam, Anoma
AU - Nigalye, Maitreyee
AU - Somsouk, Ma
AU - Schacker, Timoty W.
AU - Sanchez, Joyce L.
AU - Hunt, Peter W.
AU - Utay, Netanya S.
AU - Lake, Jordan E.
N1 - Publisher Copyright:
© Pathogens and Immunity 2017.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Fibrosis
KW - GALT
KW - HIV
KW - Immune reconstitution
UR - http://www.scopus.com/inward/record.url?scp=85107496728&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85107496728&partnerID=8YFLogxK
U2 - 10.20411/pai.v2i2.180
DO - 10.20411/pai.v2i2.180
M3 - Article
AN - SCOPUS:85107496728
SN - 2469-2964
VL - 2
SP - 239
EP - 252
JO - Pathogens and Immunity
JF - Pathogens and Immunity
IS - 2
ER -