title: Idiopathic CD4 lymphocytopenia: clinical and immunologic characteristics and follow-up of 40 patients.
abstract: Idiopathic CD4 T lymphocytopenia (ICL) is a rare and severe condition with limited available data. We conducted a French multicenter study to analyze the clinical and immunologic characteristics of a cohort of patients with ICL according to the Centers for Disease Control criteria.We recruited 40 patients (24 female) of mean age 44.2 ± 12.2 (19-70) years. Patients underwent T-lymphocyte phenotyping and lymphoproliferation assay at diagnosis, and experiments related to thymic function and interferon (IFN)-γ release by natural killer (NK) cell were performed. Mean follow-up was 6.9 ± 6.7 (0.14-24.3) years. Infectious, autoimmune, and neoplastic events were recorded, as were outcomes of interleukin 2 therapy.In all, 25 patients had opportunistic infections (12 with human papillomavirus infection), 14 had autoimmune symptoms, 5 had malignancies, and 8 had mild or no symptoms. At the time of diagnosis, the mean cell counts were as follows: mean CD4 cell count: 127/mm (range, 4-294); mean CD8: 236/mm (range, 1-1293); mean CD19: 113/mm (range, 3-547); and mean NK cell count: 122/mm (range, 5-416). Most patients had deficiency in CD8, CD19, and/or NK cells. Cytotoxic function of NK cells was normal, and patients with infections had a significantly lower NK cell count than those without (p = 0.01). Patients with autoimmune manifestations had increased CD8 T-cell count. Proliferation of thymic precursors, as assessed by T-cell rearrangement excision circles, was increased. Six patients died (15%). CD4 T-cell count <150/mm and NK cell count <100/mm were predictors of death.In conclusion, ICL is a heterogeneous disorder often associated with deficiencies in CD8, CD19, and/or NK cells. Long-term prognosis may be related to initial CD4 and NK cell deficiency.
authors.affiliation: From the Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Cochin, Service de Médecine Interne, Paris (AR, BT, LG, LM); Institut Cochin, U016, CNRS, UMR8104, Université Paris Descartes, Sorbonne Paris Cité 22, Paris (AR, RC, BC-DM, LM); UPMC, Université Paris 6 and INSERM, UMR945, AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris (BA, GC, PH, PD); Université Paris 13 and AP-HP, Département de Médecine Interne, Hôpital Avicenne, Bobigny (AK); Université Paris Diderot and AP-HP, Département d'Immunologie Clinique, Hôpital Saint-Louis, Paris (EO); UPMC, Université Paris 6 and AP-HP, Hôpital Pitié-Salpêtrière, Service de Médecine Interne, Paris (NC-C); Université Paris Descartes and AP-HP, Service de Maladies Infectieuses, Hôpital Necker-Enfants Malades, Paris (OL); and Université Paris Descartes and AP-HP, Service de Dermatologie, Hôpital Cochin, Paris (ND); France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Régent
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
authors.forename: Guislaine
authors.initials: G
authors.lastname: Carcelain
authors.forename: Rémi
authors.initials: R
authors.lastname: Cheynier
authors.forename: Benjamin
authors.initials: B
authors.lastname: Terrier
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Charmeteau-De Muylder
authors.forename: Alain
authors.initials: A
authors.lastname: Krivitzky
authors.forename: Eric
authors.initials: E
authors.lastname: Oksenhendler
authors.forename: Nathalie
authors.initials: N
authors.lastname: Costedoat-Chalumeau
authors.forename: Pascale
authors.initials: P
authors.lastname: Hubert
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupin
authors.forename: Patrice
authors.initials: P
authors.lastname: Debré
authors.forename: Loïc
authors.initials: L
authors.lastname: Guillevin
authors.forename: Luc
authors.initials: L
authors.lastname: Mouthon
mesh_terms: D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008231:Lymphopenia / Q000150:complications* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D013950:Thymus Gland / Q000503:physiopathology
chemical_list: D007371:Interferon-gamma