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Sex-specific cytokine, chemokine, and growth factor signatures in T1D patients and progressors
Boston Coll, MA 02467 USA.
Boston Coll, MA 02467 USA.
Boston Coll, MA 02467 USA.
Univ Florida, FL USA; Univ Florida, FL USA.
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2024 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 38, no 24, article id e70270Article in journal (Refereed) Published
Abstract [en]

Numerous studies have reported altered cytokine levels in type 1 diabetes (T1D) patients, yet findings remain inconsistent. In this pilot study, we tested the hypothesis that circulating immune markers exhibit sex-based differences in T1D, both prior to and after disease onset. We analyzed 47-48 cytokine, chemokine, and growth factor levels in two cohorts. To assess post-disease differences, we analyzed serum samples from 25 controls and 25 T1D patients. To examine pre-disease progression, we utilized samples from 21 control children and 16 T1D progressors, collected at age 5 years before disease onset. Across all T1D patients and controls, only macrophage colony-stimulating factor and interleukin (IL)-6 showed significant differences. However, we identified notable alterations when comparing sex-age-matched controls and T1D samples. Female T1D patients exhibited lower levels of inflammatory cytokines (tumor necrosis factor-alpha, IL-6, IL-1a), Th2 cytokines (IL-4, IL-13), and chemokines (macrophage inflammatory protein (MIP)-1 alpha, regulated upon activation, normal T cell expressed and secreted, MIP-3) compared to female controls, differences that were not observed in males. Notably, IL-22 was lower in female T1D patients compared to female controls, whereas it was higher in male T1D patients compared to male controls. Male T1D patients showed elevated levels of growth factors (epidermal growth factor, platelet-derived growth factor-AB/BB) compared to male controls. In T1D progressors, growth-regulated alpha was lower compared to controls in both sexes. Multiple regression analysis further revealed associations between cytokine levels and factors such as age, BMI, and breastfeeding duration. Overall, our findings serve as a proof of concept, highlighting the importance of sex-specific differences in T1D pathogenesis. However, follow-up studies with larger sample sizes are needed to validate and generalize these results.

Place, publisher, year, edition, pages
WILEY , 2024. Vol. 38, no 24, article id e70270
Keywords [en]
autoimmunity; chemokine; cytokine; growth factor; sex; type 1 diabetes
National Category
Pediatrics
Identifiers
URN: urn:nbn:se:liu:diva-210722DOI: 10.1096/fj.202402354RISI: 001380341500001PubMedID: 39704278Scopus ID: 2-s2.0-85212682066OAI: oai:DiVA.org:liu-210722DiVA, id: diva2:1926117
Note

Funding Agencies|Beatson Foundation; Manpei Suzuki Diabetes Foundation; Diabetes Research Connection (DRC); National Institute of Health [P01 AI042288]; Swedish Research Council [K2005-72X-11242-11A, K2008-69X-20826-01-4]; Child Diabetes Foundation; JDRF Wallenberg Foundation [K 98-99D-12813-01A]; Medical Research Council of Southeast Sweden; Swedish Council for Working Life and Social Research [FAS2004-1775]; Ostgoeta Brandstodsbolag; ALF grants from Region OEstergoetland and Linkoeping University, Sweden; Joanna Cocozza Foundation

Available from: 2025-01-10 Created: 2025-01-10 Last updated: 2025-01-10

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Ludvigsson, Johnny
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Division of Children's and Women's HealthFaculty of Medicine and Health SciencesH.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus
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