ABSTRACT
Taking into consideration the multiparametric nature of systemic lupus erythematosus (SLE), the severity and variability of symptoms and the lack of effective therapeutic approaches, this study took advantage of the recently described role of soluble major histocompatibility complex class II (sMHCII) molecules in maintaining tolerance to the organism and attempted to apply sMHCII proteins as a treatment to murine SLE experimental models in vitro as well as in vivo. After breaking tolerance to DNA in vitro, which was accompanied by development of specific anti-dsDNA antibodies, syngeneic or allogeneic sMHCII molecules, purified from healthy mouse serum, could significantly reduce the specific antibody levels and drive the system towards immunosuppression, as assessed by specific marker analysis on T cells and cytokine production by flow cytometry and ELISA, respectively. The in vivo experimental model consisted of pristane-induced SLE symptoms to BALB/c mice, which developed maximal levels of anti-dsDNA 2 months after pristane inoculation. Syngeneic or allogeneic sMHCII administration could alleviate pristane-induced symptoms, significantly decrease specific anti-dsDNA antibody production and develop immunosuppression to the host, as manifested by increase of CD4 + CTLA-4 + and CD4 + CD25 + cell populations in the spleen. Thus, the results presented in this study introduced the ability of sMHCII proteins to suppress specific autoantigen response, opening new areas of research and offering novel therapeutic approaches to SLE with expanding features to other autoimmune diseases.
Subject(s)
Antibodies, Antinuclear/immunology , Autoantigens/immunology , Histocompatibility Antigens Class II/immunology , Immune Tolerance/immunology , Immunotherapy/methods , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/therapy , T-Lymphocytes/immunology , Animals , CD4 Antigens/metabolism , CTLA-4 Antigen/metabolism , Cells, Cultured , DNA/immunology , Disease Models, Animal , Immunosuppression Therapy , Interleukin-2 Receptor alpha Subunit/metabolism , Lupus Erythematosus, Systemic/chemically induced , Mice , Mice, Inbred BALB C , Spleen/cytology , Spleen/immunology , Terpenes/adverse effectsABSTRACT
We describe a patient in whom an initially intact sciatic nerve became rapidly encased in heterotopic bone formed in the abductor compartment after reconstruction of the posterior wall of the acetabulum following fracture. Prompt excision and neural release followed by irradiation and administration of indometacin resulted in a full neurological recovery and no recurrence 27 months later.
Subject(s)
Acetabulum/injuries , Hip Dislocation/surgery , Nerve Compression Syndromes/etiology , Ossification, Heterotopic/complications , Postoperative Complications/etiology , Sciatic Nerve , Accidental Falls , Acetabulum/diagnostic imaging , Acetabulum/surgery , Adult , Fracture Fixation, Internal , Humans , Male , Ossification, Heterotopic/therapy , Paresthesia/etiology , Paresthesia/therapy , Postoperative Complications/therapy , Radiography , Recovery of Function , Time Factors , Young AdultABSTRACT
Trauma patients often present in a state of haemorrhagic shock. Blood products remain the gold standard of resuscitation, but allogeneic blood transfusions (ABTs) are associated with several risks. The stimulating effect of recombinant-erythropoietin (EPO-A) on erythropoiesis has raised interest in its administration as an alternative. The existing evidence on the early use of EPO-A in the acute phase of trauma patients management consists of only 14 publications. The level of evidence of these studies and the number of treated patients was not found to be adequate to support its generalised use, despite their favourable results. Its safety profile, the preliminary proofs of its efficacy, and the additional cyto-protective properties of EPO-A strongly encourage further controlled studies assessing its use in the acute setting of initial trauma management.
