1217 Carbone, et al: Immunophenotype in APS Personal non-commercial use only. The Journal of Rheumatology Copyright © 2009. All rights reserved. Quantitative Abnormalities of Peripheral Blood Distinct T, B, and Natural Killer Cell Subsets and Clinical Findings in Obstetric Antiphospholipid Syndrome JAVIER CARBONE, ANTONIO GALLEGO, NALLIBE LANIO, JOAQUIN NAVARRO, MARIA ORERA, ANGELAGUARON, EDUARDO FERNANDEZ-CRUZ, and ELIZABETH SARMIENTO ABSTRACT. Objetive. Few studies have assessed immunophenotypic abnormalities on lymphocyte subsets in patients with antiphospholipid syndrome (APS). We performed an extended immunological study to define alterations of distinct T, B, and natural killer (NK) cell subsets in obstetric patients with APS and their relationship with APS–associated complications. Methods. Patients and controls: 36 women with APS [Sydney criteria, Group A1 without thrombo- sis (n = 26), Group A2 with thrombosis (n = 10)]; and 36 age matched women with recurrent abor- tion without antiphospholipid antibodies (disease controls; Group B), 36 healthy parous women (healthy controls; Group C), and 36 healthy nonparous women (healthy controls; Group D). Thrombotic events occurred after history of abortions in all A2 women. Three-color whole-blood flow cytometry was used to characterize the distinct immunophenotypes. Results. A1 patients had significantly higher percentages of CD4+CD45RA–CCR7+ central memo- ry cells (A1 vs D), higher percentages of activated CD4+CD25+ T cells (A1 vs D), and lower per- centages and absolute counts of CD4+CD45RA–CCR7– effector memory cells (A1 vs D). Group A2 patients had higher percentages and absolute numbers of CD19+CD27–IgD+ naive B cells (A2 vs A1 vs all controls), lower percentages and absolute numbers of CD3–CD56+CD16+ NK cells (A2 vs all controls), and higher percentages of activated CD4+DR+ (A2 vs all controls), CD8+DR+ (A2 vs A1 vs C vs D), CD4+CD38+DR+ (A2 vs D), and CD4+CD25+DR+ T cells (A2 vs all controls). Increased percentages of CD8+DR+ T cells [relative risk (RR) 2.43, 95% CI 1.09–5.44, p = 0.02] and of naive B cells (RR 3.05, 95% CI 1.30–7.11, p = 0.009) were associated with development of thrombosis. Conclusion. In obstetric patients with APS we documented significant changes in T, B, and NK cell homeostasis. Increased levels of CD8+DR+ and CD19+CD27–IgD+ cells might identify obstetric patients with APS at risk of having thrombosis. (First Release April 1 2009; J Rheumatol 2009;36:1217–25; doi:10.3899/jrheum.081079) Key Indexing Terms: ANTIPHOSPHOLIPID SYNDROME IMMUNE SYSTEM B LYMPHOCYTES OBSTETRICS From the Reproductive Immunology Group, Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain. Supported by a grant from Fundación Salud 2000, Madrid, Spain, to Dr. Carbone. J. Carbone, PhD; A. Gallego, PhD; N. Lanio, PhD; J. Navarro, PhD; M. Orera, MD; A. Aguaron, MD; E. Fernandez-Cruz, PhD; E. Sarmiento, PhD, Reproductive Immunology Group, Immunology Department, Hospital General Universitario Gregorio Marañon. Address reprint requests to Dr. J. Carbone, Clinical Immunology Unit, Immunology Department, Hospital General Universitario Gregorio Marañón, Dr. Esquerdo 46, 28007, Madrid, Spain. E-mail: jcarbone.hgugm@salud.madrid.org Accepted for publication December 15, 2008. Antiphospholipid antibodies (aPL) are a risk factor for recurrent abortion and obstetrical complications 1 . Twenty-five years after the description of the disease, the mechanisms of aPL-mediated pregnancy failure are incom- pletely understood and some issues of management of preg- nant women remain unsolved 2 . It has been suggested that antiphospholipid syndrome (APS) has some pathogenic fea- tures of an inflammatory disease, rather than being only a prothrombotic state 3 . aPL are associated with thrombotic events but these cannot explain all the abortion events. Recent experimental and clinical evidence of an associated inflammatory condition in APS include adhesion molecule expression, complement activation, or proinflammatory cytokine/chemokine secretion 4-6 . Autoreactive CD4+ T cells to ß 2 -glycoprotein I (ß 2 -GPI) that promote production of pathogenic aPL have also been identified 7-9 . Few studies have assessed the presence of immunophe- notypic abnormalities on peripheral blood lymphocyte sub- sets in APS 10-14 . In a B cell-induced autoimmune disease we still lack basic information such as the distribution of naive www.jrheum.org Downloaded on December 14, 2021 from