Andrea Picchianti Diamanti1, M Manuela Rosado2, Marco Scarsella2, Sara Ceccarelli3, Bruno Laganà4, Raffaele D'Amelio4, Rita Carsetti5. 1. "Sapienza" University of Rome, II School of Medicine, S. Andrea University Hospital, Chair and Division of Allergy, Clinical Immunology and Rheumatology, Rome, Italy pyke@inwind.it. 2. Immunology Unit, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Rome, Italy. 3. Immunology Unit, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Rome, Italy Liver Research Unit, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Rome, Italy. 4. "Sapienza" University of Rome, II School of Medicine, S. Andrea University Hospital, Chair and Division of Allergy, Clinical Immunology and Rheumatology, Rome, Italy. 5. Immunology Unit, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Rome, Italy Diagnostic Immunology Unit, Department of Laboratories, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Rome, Italy.
Abstract
BACKGROUND: Primary immunodeficiencies (PIDs) are generally characterized by recurrent infections; however they may be complicated by other clinical disorders such as allergy, autoimmunity, and lymphoproliferation. In particular, autoimmunity may be the first manifestation of the disease in patients with low serum immunoglobulins (Ig) levels. Here we describe a group of patients that share features of immunodeficiency and autoimmunity. MATERIALS AND METHODS: All patients went through a complete T and B cell subset characterization and a B cell function analysis in the peripheral blood by flow-cytometry. B cell proliferation and plasma cell differentiation was measured, in vitro, after CpG stimulation for 7 days as previously described. Semi-quantitative PCR analysis for AID and UNG expression as well as serum levels of BAFF were carried out in order to better define the diagnosis. RESULTS: Immunological and molecular analysis did not lead to the identification of known molecular defect typical of Hyper IgM syndrome. A comparative study of the peripheral blood B cell subsets between patients and healthy donors showed that in patients with autoimmune manifestations all circulating B cells expressed high amounts of surface IgM. CONCLUSIONS: These results suggest that the increased IgM expression on circulating B cells, reflecting B cell activation, might identify a clinical condition characterized by hyper IgM serum levels of unknown molecular defects, associated with susceptibility to infections and autoimmunity.
BACKGROUND:Primary immunodeficiencies (PIDs) are generally characterized by recurrent infections; however they may be complicated by other clinical disorders such as allergy, autoimmunity, and lymphoproliferation. In particular, autoimmunity may be the first manifestation of the disease in patients with low serum immunoglobulins (Ig) levels. Here we describe a group of patients that share features of immunodeficiency and autoimmunity. MATERIALS AND METHODS: All patients went through a complete T and B cell subset characterization and a B cell function analysis in the peripheral blood by flow-cytometry. B cell proliferation and plasma cell differentiation was measured, in vitro, after CpG stimulation for 7 days as previously described. Semi-quantitative PCR analysis for AID and UNG expression as well as serum levels of BAFF were carried out in order to better define the diagnosis. RESULTS: Immunological and molecular analysis did not lead to the identification of known molecular defect typical of Hyper IgM syndrome. A comparative study of the peripheral blood B cell subsets between patients and healthy donors showed that in patients with autoimmune manifestations all circulating B cells expressed high amounts of surface IgM. CONCLUSIONS: These results suggest that the increased IgM expression on circulating B cells, reflecting B cell activation, might identify a clinical condition characterized by hyper IgM serum levels of unknown molecular defects, associated with susceptibility to infections and autoimmunity.
Authors: Lucía Del Pino-Molina; Eduardo López-Granados; Quentin Lecrevisse; Juan Torres Canizales; Martín Pérez-Andrés; Elena Blanco; Marjolein Wentink; Carolien Bonroy; Jana Nechvatalova; Tomas Milota; Anne-Kathrin Kienzler; Jan Philippé; Ana E Sousa; Mirjam van der Burg; Tomas Kalina; Jacques J M van Dongen; Alberto Orfao Journal: Front Immunol Date: 2021-02-17 Impact factor: 7.561