Chronic Granulomatous Disease (Cgd) in a Black Family With Atypical Genetic Transmission

Abstract

When 1ynphoc;tes and m a c r o p f y e m w a n milk were coc u l t u r e d , s i g n i f i c a n t l y g r e a t e r amounts of IgA and IgM were found than when lymphocytes were cultured alone. To determine whether t h e breastmilk macroohaae was r e a u l a t i n a lvmihocvte synthesis o r i t s e l f r e l e a s i n g i k u n o g l o b~l i n , & l t u r & macrophages and lymphocytes from t h e f r e s h milk of 33 healthy mothers. The c e l l u l a r components were i s o l a t e d by c e n t r i f u g a t i o n and t h e lymphocytes separated from t h e g l a s s adherent macrophages by overnight incubation i n g l a s s f l a s k s . &he r e l e a s e of IgA,IgM,and IgG I n t o 1 ml o f culture media by 2x10 lymphocytes o r macrophages was o u a n t i t a t e d using double antibody radioimnunoassays. In 7 day lymphocyte c u l t u r e s mean IgA, Igb!, and IgG released was 358, 46 and 11 ng/ml r e s p e c t i v e l y . Mean IgA. IgM, and IgG r eleased i n macrophage c u l t u r e s was 9089. 319, and 9 ng/ml respecti v e l y . To d e t e r n i n e whether t h e imnunoglobul i n present In macrophages from 6 mothers were both c u l t u r e d f o r 7 days and on day one sonicated. Sonicates were u l t r a c e n t r i f u g e d and imnunoglobulins In t h e supernatant and p e l l e t were measured. The i n u n o g l o b u l i n content of the supernatant following s o n i c a t l o n o f macrophages was s i g n i f i c a n t l y g r e a t e r than both t h a t bound t o t h e c e l l p e l l e t ( p < .05) and t h a t of t h e 7 day c u l t u r e ( p < .05). These d a t a i n d i c a t e t h a t t h e breastmilk macrophage r e l e a s e s s i g n i f i c a n t l y more imunoblobulin than does t h e lymphocyte ( p <,.02) and t h a t i t may serve a s a t r a n s p o r t vehicle capable o f delayed imnunoglobulln r e l e a s e . P a t i e n t s with combined immunodeficiency (CID) and adenosine deaminsse (ADA) deficiency may have low o r absent ADA a c t i v i t y i n v a r i o u s t i s s u e s . Hirschhorn e t a l . have shown t h a t t h e a c t i v i t y i n p a t i e n t f i b r o b l a s t s is a mutant form of ADA (PNAS 73: 213. 1976). Others have suggested t h a t t h e deficiency r e f l e c t s an inh i b i t i o n of ADA ( T r o t t a e t e l . . PNAS 73: 104, 1976). W e have is* l a t e d and i n p a r t c h a r a c t e r i z e d p r o p e r t i e s of t h e r e s i d u a l ADA from spleen of one p a t i e n t . Radioinmunoassay f o r ADA p r o t e i n i n e r y t h r o c y t e s and s p l e e n e x t r a c t s of t h e p a t i e n t showed no crossr e a c t i n g protein. Chromatography of ADA-CID s p l e e n e x t r a c t s produced a f r a c t i o n with adenosine deaminating a c t i v i t y which could n o t be adsorbed on a f f i n i t y o r anti-ADA columns. The deaminating a c t i v i t y could n o t be i n h i b i t e d w i t h erythro-9-(2-hydroxy1-3- 1% of t h e t o t a l ADA a c t i v i t y , was i s o l a t e d from normal spleen ext r a c t s . W e conclude t h a t t h e adenosine deami...