muramidase and Graft-vs-Host-Disease

To assess the efficacy of topical cyclosporine 0.05% (Restasis) in patients with dry eye associated with graft versus host disease after stem cell transplantation.. After completing a 3-month run-in period of using only artificial tears to control dry eye symptoms in both eyes, patients who failed to achieve adequate relief (n = 8) were instructed to instill topical cyclosporine twice a day. Visual acuity, slit-lamp appearance, and intraocular pressure were evaluated every 2 weeks for a minimum of 3 months. In addition, Schirmer basal secretion tests, noninvasive fluorescein breakup time, and tear lysozyme were also performed. Patients were also given a dry eye questionnaire regarding symptoms of burning, tearing, and blurred vision.. Dry eye signs improved significantly with cyclosporine treatment in 7 of 8 patients. Cyclosporine provided statistically significant improvements in Schirmer basal secretion scores (P = 0.003), tear breakup time (P = 0.002), and tear lysozyme levels (P = 0.033) after 3 months of treatment.. The findings in this prospective study suggest that dry eye associated with graft versus host disease can be effectively treated with topical cyclosporine, especially in patients unresponsive to other treatment modalities. These findings should be further evaluated in large-scale, controlled clinical trials.

Topics: Administration, Topical; Adult; Cyclosporine; Dry Eye Syndromes; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Male; Middle Aged; Muramidase; Prospective Studies; Surveys and Questionnaires; Tears; Treatment Outcome; Visual Acuity

Acute graft-versus-host disease (aGVHD) is a lethal complication after allogeneic hematopoietic stem cell transplantation. The mechanism involves the recognition of host antigens by donor-derived T cells which induces augmented response of alloreactive T cells. In this study, we characterized the role of a previously identified novel classical secretory protein with antitumor function-LYG1 (Lysozyme G-like 1), in aGVHD. LYG1 deficiency reduced the activation of CD4

Topics: Allografts; Animals; Cell Line, Tumor; Cell Polarity; Disease Models, Animal; Graft vs Host Disease; Graft vs Tumor Effect; Hematopoietic Stem Cell Transplantation; Humans; Interferon-gamma; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Muramidase; Recombinant Proteins; Signal Transduction; T-Lymphocytes, Regulatory; Transplantation, Homologous

B cell autoreactivity is a component of chronic graft versus host (GVH) disease in humans and mice. Chronic GVH driven by I-A disparity results in loss of B cell tolerance in Ig/sHEL tolerant mice. In these mice, B cell anergy is characterized by down-modulation of sIgM mediated by intracellular retention in the endoplasmic reticulum (ER) and/or a block in post-ER processing of IgM receptors. Here, we report that GVH induces a selective increase in post-ER processing of the micro chain and trafficking to the cell surface of IgM receptors in B cells that bind HEL self-antigen. The increase in sIgM was detectable as early as 6 days post-GVH, before the appearance of circulating autoantibodies, and was particularly prominent in B cells that up-regulated surface I-A. A further increase in sIgM was found at later time points, along with circulating anti-HEL autoantibodies and a marked decrease in serum-free HEL, but no significant change in the amounts of HEL bound to B cells in vivo. These findings suggest that (i) abrogation of ER retention of IgM receptors in self-reactive B cells is an early event triggered by allogeneic T cells and (ii) at later stages of GVH disease the appearance of autoantibodies reduces the availability of free autoantigen, which may further escalate anergy escape of self-reactive B cells, and lead to exacerbation and perpetuation of autoimmunity.

Topics: Adoptive Transfer; Animals; Antigen-Antibody Complex; Antigens, CD; Autoantibodies; Autoimmunity; B-Lymphocytes; B7-2 Antigen; Blotting, Western; Bone Marrow Cells; CD24 Antigen; Chronic Disease; Clonal Anergy; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Graft vs Host Disease; Hexosaminidases; Histocompatibility Antigens Class II; Immunoglobulin D; Immunoglobulin mu-Chains; Leukocyte Common Antigens; Lymphocyte Activation; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muramidase; Protein Processing, Post-Translational; Protein Transport; Receptors, Antigen, B-Cell; Receptors, Fc; Receptors, IgE; Spleen

Topics: Animals; Animals, Newborn; Antibody Formation; Antigens; Cats; Cell-Free System; Female; Graft vs Host Disease; Humans; Male; Methods; Mice; Muramidase; Rats; Rats, Inbred Strains; Tissue Extracts