Hyper-IgM, neutropenia, mild infections and low response to polyclonal stimulation: hyper-IgM syndrome or common variable immunodeficiency?
A young woman presenting respiratory infections, polyarthritis, severe neutropenia, and increased serum IgM was treated with intravenous immunoglobulin (IVIG) with good clinical and laboratory outcome followed by a loss of efficacy. The increased serum IgM associated to recurrent infections and autoimmune manifestations suggested the diagnosis of a hyper-IgM syndrome (HIGMs). The frequency of peripheral T cells, the expression of CD40 on the patients' B cells and CD40L on T cells and the activation-induced cytidine deaminase (AID) and uracil-DNA glycosylase (UNG) at mRNA level was comparable to controls. In contrast, the frequency of B cells was one half of the healthy control and all cells showed an atypical phenotype. Although AID and UNG were normal, class-switch recombination was not very efficient because circulating switched memory were reduced and, once stimulated with CpG, generated less antibody-secreting cells than controls. An increase in serum B Lymphocytes stimulator (BLyS) was also found. The patient presented a peculiar clinical and immunological phenotype fitting for many aspects of both HIGM4 and Common Variable Immunodeficiency (CVID). These findings underline the need to better explore the complex link between these two diseases.
Research Center, Ospedale Pediatrico Bambino Gesù, Laboratory of Flow-cytometry and B cell development, IRCSS, Rome, Italy.
M M
MM
Rosado
A
A
Picchianti Diamanti
S
S
Cascioli
S
S
Ceccarelli
S
S
Caporuscio
R
R
D'Amelio
R
R
Carsetti
B
B
Lagana
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D017074:Common Variable Immunodeficiency / Q000150:complications / Q000175:diagnosis* / Q000276:immunology* / Q000628:therapy; D018899:CpG Islands / Q000276:immunology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D053306:Hyper-IgM Immunodeficiency Syndrome / Q000150:complications / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy; D007075:Immunoglobulin M / Q000097:blood*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use; D016130:Immunophenotyping; D009503:Neutropenia / Q000276:immunology* / Q000628:therapy; D010641:Phenotype; D011237:Predictive Value of Tests; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation
D015415:Biomarkers; D007075:Immunoglobulin M; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors