Brief Det'initive Report - Europe PMC

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The increased frequencies of the B cell alloantigens DR2, DR3, and MT1 in ... indicate that normals with a haplotype containing either HLA-DR2, -MT1, or -B8/.
Brief Det'initive Report

IMPAIRED Fc-MEDIATED MONONUCLEAR

PHAGOCYTE

S Y S T E M C L E A R A N C E IN H L A - D R 2 A N D M T 1 - P O S I T I V E H E A L T H Y Y O U N G ADULTS* BY R O B E R T P. KIMBERLY,~ ALLAN GIBOFSKY,§ JANE E. SALMON,][ AND MARILENA FOTINO

From the Department of Medicine, The Hospital for Special Surgery and The New York HospitaLCornell Medical Center, and The New York Blood Center, New York 10021 T h e increased frequencies o f the B cell alloantigens D R 2 , D R 3 , a n d M T 1 in systemic lupus e r y t h e m a t o s u s (SLE) have suggested that genes influencing either disease susceptibility or expression are located in or n e a r the m a j o r h u m a n histocomp a t i b i l i t y H L A c o m p l e x on c h r o m o s o m e 6 in m a n (1-3) a n d have raised the possibility t h a t some i m m u n o l o g i c a b n o r m a l i t i e s t h a t occur in disease could be associated w i t h the genetic m a r k e r per se r a t h e r t h a n be solely a reflection of the disease process. M a r k e d i m p a i r m e n t o f Fc r e c e p t o r - d e p e n d e n t m o n o n u c l e a r p h a g o c y t e system (MPS) clearance occurs in S L E (4, 5). N o r m a l s with the H L A - B 8 / D R 3 p h e n o t y p e m a y also have d e l a y e d M P S clearance (6). Since M P S - c l e a r a n c e dysfunction m i g h t reflect at least in p a r t an intrinsic cellular defect, we e x a m i n e d the Fc receptorm e d i a t e d M P S c l e a r a n c e a n d in vitro m o n o c y t e function in disease-free y o u n g a d u l t s with the o t h e r H L A antigens seen with increased frequency in SLE. O u r results i n d i c a t e t h a t n o r m a l s with a h a p l o t y p e c o n t a i n i n g either H L A - D R 2 , - M T 1 , or - B 8 / D R 3 have i m p a i r e d M P S clearance c o m p a r e d with their o t h e r n o r m a l controls. Fcd e p e n d e n t phagocytosis b y circulating monocytes was also i m p a i r e d in the D R 2 a n d M T 1 groups.

Materials and Methods Subjects. 10 female and 29 male disease-free Caucasian adults participated in the MPSclearance study after giving written informed consent. 4 female and 13 males were donors for in vitro studies. No subject had a family history of SLE or other autoimmune disease sharing the HLA associations seen in SLE. Protocols for all studies were approved by the institutional Committees on Human Rights in Research. Histocompatibility Antigen Determination. Histocompatibility testing (HLA) for serologically detectable antigens of the A, B, C, DR, and MT series was performed on isolated mononuclear cells and nylon wool-separated B lymphocytes as described (1). MPS Fc Receptor-mediatedClearance Studies. Fc receptor-mediated MPS studies were done by previously described techniques (4, 5). Cell Preparation. Mononuctear cells were separated by density centrifugation on FicoliHypaque and purified for aggregate-binding and rosette-formation assays by adherence to * Supported by grant AM 14627 from the National Institutes of Health and a grant from the S.L.E. Foundation, Inc., New York. :~Andrew W. Mellon Teacher Scientist. § Recipient of Clinical Investigator Award AM 00673. IIFellow of the S.L.E. Foundation, Inc., New York.

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J. ExP. MEB. © The Rockefeller University Press • 0022-1007/83/05/1698/06 $1.00 Volume 157 May 1983 1698-1703

KIMBERLY ET AL.

BRIEF DEFINITIVE REPORT

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plastic surfaces (7). 1 × 10n peroxidase-positive cells in RPMI 1640 with 20% gammaglobulinfree fetal calf serum (FCS) (Gibco Laboratories, Grand Island, NY) were plated onto a disposable plastic dish (Falcon Labware, Oxnard, CA) that had been precoated overnight with heat-inactivated FCS containing