UNLABELLED: Hyper-IgM syndromes are characterized by normal or elevated serum IgM levels with the absence or reduced levels of other immunoglobulins. There are some patients with defective class-switch recombination (CSR) who do not have CD40L, CD40, AID, and UNG defects. The aim of this study is to determine the B-cell functions of patients with Hyper-IgM type 4 phenotype. Ten patients (seven males and three females) 84.2 ± 16.5 months of age with initial low serum IgG and IgA and high or normal IgM levels were included. Clinically, 50% had recurrent upper respiratory tract, 10% urinary tract, 10% lower respiratory tract infections, and 30% had mixed type infections. Lymphoid hyperplasia, overt autoimmune manifestations, or malignancy was not noted. Seven of 10 patients were studied twice; at the age of 34.2 ± 13.7 and at 86.6 ± 12.3 months. Absolute lymphocyte counts and lymphocyte subsets were normal in all cases. All of them had normal expression of CD40 on B cells and CD40L on activated T cells for males. At first examination, all patients had normal in vitro sCD40L+rIL-4-induced B cell proliferation response and somatic hypermutation but CSR towards IgE was absent. AID and UNG genes did not show any abnormalities. All showed improvement in both clinical findings and Ig levels during the follow-up period of 55.8 ± 14.8 months. Ages for normalization of IgG and IgA were 68.2 ± 8.7 and 70.2 ± 21.6 months, respectively. During the second evaluation: In vitro sCD40L+rIL-4-induced B-cell proliferation was normal in all cases, whereas CSR was still abnormal in five of eight patients. Two of the patients had an increase in in vitro CSR response but still low IgG2 subclass levels. Three patients with initially absent in vitro CSR response also normalized. CONCLUSION: Clinical manifestations and immunoglobulin levels of the patients with Hyper-IgM type 4 phenotype recovered in late childhood at about 6 years of age. There was a transient CSR defect which was not observed in cases with transient hypogammaglobulinemia of infancy. Detection of a non-AID or non-UNG associated CSR defect in infancy should be confirmed later on since spontaneous recovery may occur.
UNLABELLED: Hyper-IgM syndromes are characterized by normal or elevated serum IgM levels with the absence or reduced levels of other immunoglobulins. There are some patients with defective class-switch recombination (CSR) who do not have CD40L, CD40, AID, and UNG defects. The aim of this study is to determine the B-cell functions of patients with Hyper-IgM type 4 phenotype. Ten patients (seven males and three females) 84.2 ± 16.5 months of age with initial low serum IgG and IgA and high or normal IgM levels were included. Clinically, 50% had recurrent upper respiratory tract, 10% urinary tract, 10% lower respiratory tract infections, and 30% had mixed type infections. Lymphoid hyperplasia, overt autoimmune manifestations, or malignancy was not noted. Seven of 10 patients were studied twice; at the age of 34.2 ± 13.7 and at 86.6 ± 12.3 months. Absolute lymphocyte counts and lymphocyte subsets were normal in all cases. All of them had normal expression of CD40 on B cells and CD40L on activated T cells for males. At first examination, all patients had normal in vitro sCD40L+rIL-4-induced B cell proliferation response and somatic hypermutation but CSR towards IgE was absent. AID and UNG genes did not show any abnormalities. All showed improvement in both clinical findings and Ig levels during the follow-up period of 55.8 ± 14.8 months. Ages for normalization of IgG and IgA were 68.2 ± 8.7 and 70.2 ± 21.6 months, respectively. During the second evaluation: In vitro sCD40L+rIL-4-induced B-cell proliferation was normal in all cases, whereas CSR was still abnormal in five of eight patients. Two of the patients had an increase in in vitro CSR response but still low IgG2 subclass levels. Three patients with initially absent in vitro CSR response also normalized. CONCLUSION: Clinical manifestations and immunoglobulin levels of the patients with Hyper-IgM type 4 phenotype recovered in late childhood at about 6 years of age. There was a transient CSR defect which was not observed in cases with transient hypogammaglobulinemia of infancy. Detection of a non-AID or non-UNG associated CSR defect in infancy should be confirmed later on since spontaneous recovery may occur.
Authors: Marcus Odendahl; Henrik Mei; Bimba F Hoyer; Annett M Jacobi; Arne Hansen; Gwendolin Muehlinghaus; Claudia Berek; Falk Hiepe; Rudi Manz; Andreas Radbruch; Thomas Dörner Journal: Blood Date: 2004-10-26 Impact factor: 22.113
Authors: Henrik E Mei; Taketoshi Yoshida; Wondossen Sime; Falk Hiepe; Kathi Thiele; Rudolf A Manz; Andreas Radbruch; Thomas Dörner Journal: Blood Date: 2008-11-05 Impact factor: 22.113
Authors: Mohamed-Ridha Barbouche; Qubo Chen; Marco Carbone; Imen Ben-Mustapha; Zakera Shums; Mehdi Trifa; Federica Malinverno; Francesca Bernuzzi; Haiyan Zhang; Nourhen Agrebi; Gary L Norman; Christopher Chang; M Eric Gershwin; Pietro Invernizzi Journal: Cell Mol Immunol Date: 2018-02-05 Impact factor: 11.530
Authors: Victoria K Tesch; Hanna IJspeert; Andrea Raicht; Daniel Rueda; Nerea Dominguez-Pinilla; Luis M Allende; Chrystelle Colas; Thorsten Rosenbaum; Denisa Ilencikova; Hagit N Baris; Michaela H M Nathrath; Manon Suerink; Danuta Januszkiewicz-Lewandowska; Iman Ragab; Amedeo A Azizi; Soeren S Wenzel; Johannes Zschocke; Wolfgang Schwinger; Matthias Kloor; Claudia Blattmann; Laurence Brugieres; Mirjam van der Burg; Katharina Wimmer; Markus G Seidel Journal: Front Immunol Date: 2018-07-02 Impact factor: 7.561