Background Adenosine deaminase (ADA) deficiency causes severe cellular and humoral immune defects and dysregulation because of metabolic toxicity. Alterations in B-cell development and function have ...been poorly studied. Enzyme replacement therapy (ERT) and hematopoietic stem cell (HSC) gene therapy (GT) are therapeutic options for patients lacking a suitable bone marrow (BM) transplant donor. Objective We sought to study alterations in B-cell development in ADA-deficient patients and investigate the ability of ERT and HSC-GT to restore normal B-cell differentiation and function. Methods Flow cytometry was used to characterize B-cell development in BM and the periphery. The percentage of gene-corrected B cells was measured by using quantitative PCR. B cells were assessed for their capacity to proliferate and release IgM after stimulation. Results Despite the severe peripheral B-cell lymphopenia, patients with ADA-deficient severe combined immunodeficiency showed a partial block in central BM development. Treatment with ERT or HSC-GT reverted most BM alterations, but ERT led to immature B-cell expansion. In the periphery transitional B cells accumulated under ERT, and the defect in maturation persisted long-term. HSC-GT led to a progressive improvement in B-cell numbers and development, along with increased levels of gene correction. The strongest selective advantage for ADA-transduced cells occurred at the transition from immature to naive cells. B-cell proliferative responses and differentiation to immunoglobulin secreting IgM after B-cell receptor and Toll-like receptor triggering were severely impaired after ERT and improved significantly after HSC-GT. Conclusions ADA-deficient patients show specific defects in B-cell development and functions that are differently corrected after ERT and HSC-GT.
Objective The present study presents a case series on the efficacy of arthrocentesis with hyaluronic acid injections for the treatment of tempreomandibular joint osteoatrhritis by providing patient ...evaluations at a one-year follow-up. Study design Twenty-five patients with a diagnosis of osteoarthritis according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD axis I group IIIb) underwent a cycle of 5 arthrocenteses with injections (1 per week) of 1 mL hyaluronic acid. A number of clinical parameters (pain at rest and mastication, masticatory efficiency, maximum nonassisted and assisted mouth openings, functional limitation, subjective efficacy, and tolerability of the treatment) were assessed by the same blinded operator at the time of the diagnosis (baseline), at each appointment during the treatment, and at 1-week, 1-month, 3-month, 6-month, and 1-year follow-up appointments. Results Descriptive analysis showed improvements which were maintained over time for all the study parameters. Permutation tests evidenced the significance of changes which occurred in many clinical parameters within the first 2 injections. Differences with baseline levels remained significant at the end of the follow-up period, particularly for the masticatory efficiency and pain at mastication (minimum and maximum) parameters. Conclusions Data from the present investigation support findings from studies on other joints, which show the efficacy of serial injections of hyaluronic acid after arthrocentesis to reduce symptoms of osteoarthritis and to maintain improvements over time.
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