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Idiopathic CD4 lymphocytopenia: clinical and immunologic characteristics and follow-up of 40 patients.

Régent A, Autran B, Carcelain G, Cheynier R, Terrier B, Charmeteau-De Muylder B, Krivitzky A, Oksenhendler E, Costedoat-Chalumeau N, Hubert P, Lortholary O, Dupin N, Debré P, Guillevin L, Mouthon L, French Idiopathic CD4 T Lymphocytopenia Study Gro - Medicine (Baltimore) (2014)

Bottom Line: Cytotoxic function of NK cells was normal, and patients with infections had a significantly lower NK cell count than those without (p = 0.01).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.

View Article: PubMed Central - PubMed

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.

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.

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Survival in 40 patients with ICL by lymphocyte subpopulation counts. Kaplan-Meier survival curves by (A) initial NK cell count and (B) combined CD4 T-lymphocyte and NK cell count.
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Figure 4: Survival in 40 patients with ICL by lymphocyte subpopulation counts. Kaplan-Meier survival curves by (A) initial NK cell count and (B) combined CD4 T-lymphocyte and NK cell count.

Mentions: Patients with infection manifestations during follow-up had a significantly lower NK cell count at diagnosis; patients with autoimmune symptoms had significantly higher CD3+, CD8+, and CD8+CD45RO+ T-cell counts; and patients with malignancy had low CD4+CD45RA+ and CD8+CD45RO+ T-cell counts (Table 5). Six patients (15%) died during follow-up. The causes of death were cerebral infection with Mycobacterium tuberculosis identified on autopsy, misdiagnosed as toxoplasmosis (P3); anaplastic lymphoma ( phenotype) (P10); pancreatic adenocarcinoma (P14); epidermoid carcinoma of the cheek (P20); respiratory failure related to pulmonary arterial hypertension (P4); and multiorgan failure due to septic shock related to Escherichia coli infection (P32). We identified initial CD4 T-cell count <150/mm3 and low NK cell count (<100/mm3) or a low NK cell count (<100/mm3) as prognostic markers of increased mortality (Figure 4).


Idiopathic CD4 lymphocytopenia: clinical and immunologic characteristics and follow-up of 40 patients.

Régent A, Autran B, Carcelain G, Cheynier R, Terrier B, Charmeteau-De Muylder B, Krivitzky A, Oksenhendler E, Costedoat-Chalumeau N, Hubert P, Lortholary O, Dupin N, Debré P, Guillevin L, Mouthon L, French Idiopathic CD4 T Lymphocytopenia Study Gro - Medicine (Baltimore) (2014)

Survival in 40 patients with ICL by lymphocyte subpopulation counts. Kaplan-Meier survival curves by (A) initial NK cell count and (B) combined CD4 T-lymphocyte and NK cell count.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4616307&req=5

Figure 4: Survival in 40 patients with ICL by lymphocyte subpopulation counts. Kaplan-Meier survival curves by (A) initial NK cell count and (B) combined CD4 T-lymphocyte and NK cell count.
Mentions: Patients with infection manifestations during follow-up had a significantly lower NK cell count at diagnosis; patients with autoimmune symptoms had significantly higher CD3+, CD8+, and CD8+CD45RO+ T-cell counts; and patients with malignancy had low CD4+CD45RA+ and CD8+CD45RO+ T-cell counts (Table 5). Six patients (15%) died during follow-up. The causes of death were cerebral infection with Mycobacterium tuberculosis identified on autopsy, misdiagnosed as toxoplasmosis (P3); anaplastic lymphoma ( phenotype) (P10); pancreatic adenocarcinoma (P14); epidermoid carcinoma of the cheek (P20); respiratory failure related to pulmonary arterial hypertension (P4); and multiorgan failure due to septic shock related to Escherichia coli infection (P32). We identified initial CD4 T-cell count <150/mm3 and low NK cell count (<100/mm3) or a low NK cell count (<100/mm3) as prognostic markers of increased mortality (Figure 4).

Bottom Line: Cytotoxic function of NK cells was normal, and patients with infections had a significantly lower NK cell count than those without (p = 0.01).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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus