In Vitro Induction of IgA Expression in Ataxia Telangiectasia (A-T) Patients with IgA Deficiency (IgAD)

Abstract

RATIONALE: To elucidate mechanisms accounting for IgAD in A-T. METHODS: Peripheral blood mononuclear cells (PBMC) of eight A-T patients with IgAD and seven normal individuals were cultured with pokeweed mitogen (PWM), soluble human trimeric CD40L ± IL-10 for 10 days. IgA and IL-10 concentrations in the supernatants were determined by ELISA. Lymphocyte subpopulations were analyzed by flow cytometry. RESULTS: A-T patients in this study had IgAD (serum IgA < 7 mg/dL) with normal IgG (1193±95 mg/dL). IgA levels in unstimulated control and patient PBMC supernatants were 341±38 and 16±12 ng/mL, respectively. CD40L alone did not induce IgA synthesis (controls 184±68; patients 7±7 ng/mL). However, CD40L combined with IL-10 induced IgA synthesis from PBMC of controls (median 3072; range 302-21760 ng/mL) and 4 of 8 patients (median 1776; range 828-2632 ng/mL). In the other four non-responder patients, there was little or no IgA production with stimulation (median 38; range 0-107 ng/mL). Those A-T patients capable of producing IgA did not differ from non-responders in terms of CD4/CD8 ratio (1.7±0.81 vs 2±0.93) or in absolute cell counts: CD4 (345±248 vs 359±74), CD19 (188±183 vs 76±65), and total lymphocyte (1411±1257 vs 988±169). PWM induced higher IL-10 production in A-T PBMCs (1903±1173; range 412-2904 pcg/mL) compared to controls (524±366; range 127-849 pcg/mL); yet, such effect failed to induce IgA production in A-T patients (24±11ng/mL). CONCLUSIONS: IgA production can be induced in PBMC from some A-T patients with IgAD. IgAD is not caused by a deficiency of IL-10 production.