Polyclonal IgG4 hypergammaglobulinemia associated with plasmacytic lymphadenopathy, anemia and nephropathy.
Marked polyclonal immunoglobulin (Ig)G4 hypergammaglobulinemia has exceptionally been reported. Here we report on two Algerian patients who presented a syndrome characterized by anemia, plasmacytic lymphadenopathy, renal manifestations, and a marked polyclonal IgG4 hypergammaglobulinemia leading to a hyperviscosity syndrome in one case. The IgG4-expressing cell percentage was significantly increased in the peripheral blood lymphocytes collected from the two patients upon diagnosis. Moreover, in contrast with normal sera, both patients' sera significantly increased the percentage of IgG4-expressing cells when incubated with CD40-stimulated normal B lymphocytes. Similar effects were obtained with the culture supernatants of the patients' activated T cells. Anti-interleukin (IL) 4 and/or anti-IL-13 antibodies were unable to antagonize the IgG4 production. IL-4 and IL-13 serum concentrations were found to be normal in the two patients. The increased IgG4 production was found to be mediated by soluble factor(s), most probably secreted by activated T cells, which did not require the signal transducer and activator of transcription 6 signaling pathway.
Boulanger
Emmanuelle
E
Department of Clinical Immunology, Hôpital Saint-Louis, AP-HP, Paris, France. emmanuelle.boulanger@sls.aphp.fr
Fuentes
Vincent
V
Meignin
Véronique
V
Mougenot
Béatrice
B
Labaume
Sylvaine
S
Gouilleux-Gruart
Valérie
V
Cogné
Michel
M
Aucouturier
Pierre
P
Clauvel
Jean-Pierre
JP
Ronco
Pierre
P
Lassoued
Kaiss
K
D000293:Adolescent; D000740:Anemia / Q000150:complications*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006942:Hypergammaglobulinemia / Q000150:complications*; D007074:Immunoglobulin G / Q000097:blood* / Q000378:metabolism; D007674:Kidney Diseases / Q000097:blood / Q000150:complications*; D008206:Lymphatic Diseases / Q000150:complications*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000473:pathology; D050800:STAT6 Transcription Factor / Q000097:blood / Q000378:metabolism
D017077:Culture Media, Conditioned; D007074:Immunoglobulin G; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human