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      Expression of T-cell Immunoglobulin- and Mucin-domain-containing Molecule-3 on Lymphocytes from Henoch-Schoenlein Purpura Patients

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          Abstract

          Objective

          To investigate T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) and its ligand galectin-9 mRNA expression in peripheral blood mononuclear cells (PBMCs) from Henoch-Schoenlein Purpura (HSP) patients.

          Methods

          Quantitative real-time reverse transcription-polymerase chain reaction (PCR) was used to examine the mRNA expression of Tim-3 and its ligand galectin-9 in PBMCs from HSP patients. ELISA methods were used to examine the levels of serum IFN-γ and immunoglobulin A1 (IgA1). The Spearman rank test was used for correlation analysis between Tim-3, galectin-9 mRNA expression and serum IFN-γ and IgA1 levels, respectively.

          Findings

          The results showed that Tim-3 and galectin-9 mRNA expression was obviously higher in patients, which was closely correlated with serum IFN-γ and IgA1, respectively.

          Conclusion

          The results suggested that Tim-3/Tim-3L may be related to the pathogenesis of HSP.

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          Most cited references5

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          Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance.

          Alberto Sanchez-Fueyo, Jane Tian, Dominic Picarella … (2003)
          Although T helper (T(H)) cell-mediated immunity is required to effectively eliminate pathogens, unrestrained T(H) activity also contributes to tissue injury in many inflammatory and autoimmune diseases. We report here that the T(H) type 1 (T(H)1)-specific Tim-3 (T cell immunoglobulin domain, mucin domain) protein functions to inhibit aggressive T(H)1-mediated auto- and alloimmune responses. Tim-3 pathway blockade accelerated diabetes in nonobese diabetic mice and prevented acquisition of transplantation tolerance induced by costimulation blockade. These effects were mediated, at least in part, by dampening of the antigen-specific immunosuppressive function of CD4(+)CD25(+) regulatory T cell populations. Our data indicate that the Tim-3 pathway provides an important mechanism to down-regulate T(H)1-dependent immune responses and to facilitate the development of immunological tolerance.
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            Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance.

            Catherine Sabatos, Sumone Chakravarti, Eugene Cha … (2003)
            T helper type 1 (T(H)1) immune responses are central in cell-mediated immunity, and a T(H)1-specific cell surface molecule called Tim-3 (T cell immunoglobulin domain, mucin domain) has been identified. Here we report the identification of a secreted form of Tim-3 that contains only the immunoglobulin (Ig) variable (V) domain of the full-length molecule. Fusion proteins (Tim-3-Ig) of both Tim-3 isoforms specifically bound CD4(+) T cells, indicating that a Tim-3 ligand is expressed on CD4(+) T cells. Administration of Tim-3-Ig to immunized mice caused hyperproliferation of T(H)1 cells and T(H)1 cytokine release. Tim-3-Ig also abrogated tolerance induction in T(H)1 cells, and Tim-3-deficient mice were refractory to the induction of high-dose tolerance. These data indicate that interaction of Tim-3 with Tim-3 ligand may serve to inhibit effector T(H)1 cells during a normal immune response and may be crucial for the induction of peripheral tolerance.
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              Effective therapy for severe Henoch-Schonlein purpura nephritis with prednisone and azathioprine: a clinical and histopathologic study.

              Alison B. Foster, V. Sharma, C. Bernard … (2000)
              To validate a scoring system to assess the severity of renal lesions and to correlate histology with clinical findings. We also examined the efficacy of treatment with prednisone (1 to 2 mg/kg/d) and azathioprine (1 to 2 mg/kg/d) for severe Henoch-Schonlein purpura (HSP) nephritis. Twenty patients were evaluated retrospectively. All underwent biopsy before treatment, and 13 underwent biopsy after therapy. We developed a scale based on glomerular, tubulointerstitial (TI), and vascular changes and assigned all specimens acuity, chronicity, and TI scores. The outcomes of 17 patients were compared with those of a historical control group. Chronicity score at initial biopsy increased with increasing delay between onset of renal involvement and first biopsy (rho = 0.55, P =.016) but did not progress after treatment was initiated. Both acuity (rho = 0.57,P =. 016) and TI (rho = 0.69, P =.003) scores correlated with clinical severity at first biopsy. The TI score correlated negatively with serum albumin (rho = -.60, P <.01). Significantly more patients in the study group than in the control group had a favorable outcome (15 [88%] of 17 vs 32 [54%] of 59, P =.011). Our scale reflects disease activity and highlights the importance of TI changes in severe HSP nephritis. Outcome comparisons indicate that early treatment with prednisone and azathioprine prevents progression of chronic changes and improves outcome.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Iran J Pediatr
                Journal ID (iso-abbrev): Iran J Pediatr
                Journal ID (publisher-id): IJPD
                Title: Iranian Journal of Pediatrics
                Publisher: Tehran University of Medical Sciences
                ISSN (Print): 2008-2142
                ISSN (Electronic): 2008-2150
                Publication date (Print): June 2013
                Volume: 23
                Issue: 3
                Pages: 345-348
                Affiliations
                [1 ]Department of Pediatrics, First Affiliated Hospital of Anhui Medical University, Hefei, China
                [2 ]Department of Medical Technology, Anhui Medical College, Hefei, China
                Author notes
                [* ] Corresponding Author: Address: Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, Hefei, China 230022. E-mail: yuanliping3986@ 123456sina.com
                Article
                Publisher ID: IJPD-23-345
                PMC ID: 3684482
                PubMed ID: 23795260
                SO-VID: 7136bb6a-0e4e-4299-9872-a7759520c7a4
                Copyright © © 2013 Iranian Journal of Pediatrics & Tehran University of Medical Sciences
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0), which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

                History
                Date received : 16 May 2012
                Date accepted : 23 January 2013
                Categories
                Subject: Short Communication

                ScienceOpen disciplines: Pediatrics
                Keywords: henoch-schoenlein purpura,t-cell immunoglobulin,mucin domain containing 3 protein,tim-3 protein,immunoglobulin a
                Data availability:
                ScienceOpen disciplines: Pediatrics
                Keywords: henoch-schoenlein purpura, t-cell immunoglobulin, mucin domain containing 3 protein, tim-3 protein, immunoglobulin a

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