Therapeutic Response to Granulocyte Colony-Stimulating Factor in a Case of Selective IgA Deficiency (SIgAD) with Chronic Neutropenia.

Neutropenia is a frequent occurrence in some immunodeficiency syndromes such as IgA deficiency, Hyper IgM syndrome, and common variable immunodeficiency¹. We present a case of an IgA-deficient patient with neutropenia treated with pegfilgrastim.

A 23-year-old Caucasian female was referred for evaluation of chronic neutropenia diagnosed at age 18 and a postpartum DVT. The patient had a history of recurrent pharyngitis since age 13 and MSSA septicemia during pregnancy. Evaluation for chronic neutropenia included negative ANA, Hepatitis panel and HIV with a normal bone marrow biopsy and no anti-granulocyte antibodies. She was found to have Protein S deficiency during her first pregnancy with no other coagulation abnormalities and was started on prophylactic doses of LMWH antepartum. Patient quit taking LMWH after delivery, had a DVT 3 weeks postpartum, and was restarted on LMWH. Quantitative immunoglobulins revealed IgA < 5 mg/dl. Peripheral blood flow cytometry showed no evidence of lymphoproliferative disorder. Bone marrow biopsy was repeated and showed a hypercellular bone marrow with no cytogenetic abnormalities. Patient was diagnosed with secondary Autoimmune neutropenia (AIN) in association with IgA deficiency. After a single dose of 6 mg pegfilgrastim, neutropenia resolved and subsequent anti-granulocyte antibodies remained negative. Patient is currently on 6mg pegfilgrastim every 2 weeks with resolution of neutropenia. Repeat Protein S level is pending.

AIN is defined as a (chronic) neutropenia in which autoantibodies against neutrophil autoantigens can be detected by leukoagglutination, neutrophil immunofluorescence, and/or monoclonal antibody immobilization of neutrophil antigens². Primary AIN is rare. Infections start 1 to 15 months after birth and recovery is spontaneous in 7 to 73 months. Neutrophil-specific autoantibodies are detectable in most patients, and are directed to NA1 or sometimes NA2. Treatment is usually not necessary. Infections are treated with antibiotics and with high-dose IVIG or G-CSF². Secondary AIN with an associated hematopoietic or systemic autoimmune disorder or with combined immunodeficiency is more frequent in adults, peaking at age 40 to 60 years is known as adult autoimmune neutropenia. Only in a few cases of adult AIN are neutrophil-antigen-specific autoantibodies found including anti-NA1, NB1, pan-Fc_RIIIb, and CD11b/CD18 (CR3) antibodies. With infections appropriate antibiotics together with G-CSF is the treatment of choice. An important effect of G-CSF is that with an increased mass of neutrophils, the autoantibodies are absorbed to the neutrophils and leading to their disappearance from the circulation².

We present a case of secondary AIN associated with IgA deficiency without demonstrable anti-neutrophil antibodies that was treated with pegfilgrastim with resolution of neutropenia. There are no published cases of IgA-deficient patients with neutropenia who received G- CSF and G-CSF may be helpful in these patients.

Off Label Use: Off label use of pegfilgrastim for treatment of autoimmune neutropenia in selective IgA deficiency..