Circulating LOXL2 Levels Reflect Severity of Intestinal Fibrosis and GALT CD4+ T Lymphocyte Depletion in Treated HIV Infection
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 c...
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| Format: | Article |
| Language: | English |
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Case Western Reserve University
2017-06-01
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| Series: | Pathogens and Immunity |
| Subjects: | |
| Online Access: | https://paijournal.com/index.php/paijournal/article/view/180 |
| _version_ | 1811339203302129664 |
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| author | Sophie Seang Anoma Somasunderam Maitreyee Nigalye Ma Somsouk Timoty W. Schacker Joyce L. Sanchez Peter W. Hunt Netanya S. Utay Jordan E. Lake |
| author_facet | Sophie Seang Anoma Somasunderam Maitreyee Nigalye Ma Somsouk Timoty W. Schacker Joyce L. Sanchez Peter W. Hunt Netanya S. Utay Jordan E. Lake |
| author_sort | Sophie Seang |
| collection | DOAJ |
| description | 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=0.007) 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. |
| first_indexed | 2024-04-13T18:22:45Z |
| format | Article |
| id | doaj.art-b25f2b285c124d359d6d79c2554d54ea |
| institution | Directory Open Access Journal |
| issn | 2469-2964 |
| language | English |
| last_indexed | 2024-04-13T18:22:45Z |
| publishDate | 2017-06-01 |
| publisher | Case Western Reserve University |
| record_format | Article |
| series | Pathogens and Immunity |
| spelling | doaj.art-b25f2b285c124d359d6d79c2554d54ea2022-12-22T02:35:23ZengCase Western Reserve UniversityPathogens and Immunity2469-29642017-06-012223925210.20411/pai.v2i2.18059Circulating LOXL2 Levels Reflect Severity of Intestinal Fibrosis and GALT CD4+ T Lymphocyte Depletion in Treated HIV InfectionSophie Seang0Anoma Somasunderam1Maitreyee Nigalye2Ma Somsouk3Timoty W. Schacker4Joyce L. Sanchez5Peter W. Hunt6Netanya S. Utay7Jordan E. Lake8Pitie Salpétrière Hospital Pierre et Marie UniversityUniversity of Texas Medical Branch, Galveston, TexasUniversity of Texas Medical Branch, Galveston, TexasUniversity of California, San Francisco, CaliforniaUniversity of Minnesota, Minneapolis, MinnesotaMayo Clinic, Rochester, MinnesotaUniversity of California, San Francisco, CaliforniaUniversity of Texas Medical Branch, Galveston, TexasUniversity of Texas Health Science Center at Houston, Houston, TexasBackground: 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=0.007) 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.https://paijournal.com/index.php/paijournal/article/view/180GALT, HIV, fibrosis, immune reconstitution |
| spellingShingle | Sophie Seang Anoma Somasunderam Maitreyee Nigalye Ma Somsouk Timoty W. Schacker Joyce L. Sanchez Peter W. Hunt Netanya S. Utay Jordan E. Lake Circulating LOXL2 Levels Reflect Severity of Intestinal Fibrosis and GALT CD4+ T Lymphocyte Depletion in Treated HIV Infection Pathogens and Immunity GALT, HIV, fibrosis, immune reconstitution |
| title | Circulating LOXL2 Levels Reflect Severity of Intestinal Fibrosis and GALT CD4+ T Lymphocyte Depletion in Treated HIV Infection |
| title_full | Circulating LOXL2 Levels Reflect Severity of Intestinal Fibrosis and GALT CD4+ T Lymphocyte Depletion in Treated HIV Infection |
| title_fullStr | Circulating LOXL2 Levels Reflect Severity of Intestinal Fibrosis and GALT CD4+ T Lymphocyte Depletion in Treated HIV Infection |
| title_full_unstemmed | Circulating LOXL2 Levels Reflect Severity of Intestinal Fibrosis and GALT CD4+ T Lymphocyte Depletion in Treated HIV Infection |
| title_short | Circulating LOXL2 Levels Reflect Severity of Intestinal Fibrosis and GALT CD4+ T Lymphocyte Depletion in Treated HIV Infection |
| title_sort | circulating loxl2 levels reflect severity of intestinal fibrosis and galt cd4 t lymphocyte depletion in treated hiv infection |
| topic | GALT, HIV, fibrosis, immune reconstitution |
| url | https://paijournal.com/index.php/paijournal/article/view/180 |
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