IgA and IgG hypogammaglobulinemia in Waldenström's macroglobulinemia.
BACKGROUND
Hypogammaglobulinemia is common in Waldenström's macroglobulinemia. The etiology of this finding remains unclear, but it has been speculated to be based on tumor-induced suppression of the 'uninvolved' immunoglobulin production


METHODS
We evaluated the incidence of IgA and IgG hypogammaglobulinemia in 207 untreated patients with Waldenström's macroglobulinemia and investigated the associated clinicopathological findings and impact of therapy. We also sequenced eight genes (AICDA, BTK, CD40, CD154, NEMO, TACI, SH2D1A, UNG) implicated in immunoglobulin deficiency in 19 Waldenström's macroglobulinemia patients with IgA and/or IgG hypogammaglobulinemia.


RESULTS
At baseline 63.3%, 58.0% and 49.3% of the 207 patients had abnormally low serum levels of IgA, IgG, or both. No association between IgA and IgG hypogammaglobulinemia and disease burden, serum IgM levels, beta(2)-microglobulin, International Prognostic Scoring System score, or incidence of recurrent infections was observed, although the presence of adenopathy and/or splenomegaly was associated with a lower incidence of hypogammaglobulinemia. Lower IgA and IgG levels were associated with disease progression in patients managed with a 'watch and wait' strategy. IgA and/or IgG levels remained abnormally low despite response to treatment, including complete remissions. A missense mutation in the highly conserved catalytic site of UNG was observed in a patient with hypogammaglobulinemia, warranting further study of this pathway in Waldenström's macroglobulinemia.


CONCLUSIONS
IgA and IgG hypogammaglobulinemia is common in Waldenström's macroglobulinemia and persists despite therapeutic intervention and response. IgA and IgG hypogammaglobulinemia does not predict the risk of recurrent infections in patients with Waldenström's macroglobulinemia, although lower levels of serum IgA and IgG are associated with disease progression in Waldenström's macroglobulinemia patients being managed with a 'watch and wait' strategy.
Hunter
Zachary R
ZR
Bing Center for Waldenström's Macroglobulinemia, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Manning
Robert J
RJ
Hanzis
Christine
C
Ciccarelli
Bryan T
BT
Ioakimidis
Leukothea
L
Patterson
Christopher J
CJ
Lewicki
Megan C
MC
Tseng
Hsuiyi
H
Gong
Ping
P
Liu
Xia
X
Zhou
Yangsheng
Y
Yang
Guang
G
Sun
Jenny
J
Xu
Lian
L
Sheehy
Patricia
P
Morra
Massimo
M
Treon
Steven P
SP
D000328:Adult; D000361:Agammaglobulinemia / Q000209:etiology* / Q000276:immunology; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007239:Infections / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D008258:Waldenstrom Macroglobulinemia / Q000150:complications* / Q000628:therapy
D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G