NCOI restriction fragment length polymorphism of the tumour necrosis factor region in systemic lupus erythematosus

Abstracts

69

#244 8.4

#245 6.2

P R O S P E C ~ V E F L O W C Y T O M E T R Y C R O S S M A T C H I N G APPEARS T O IMPROVE G R A F T

SURVIVAL IN HIGH PRA AND REGRAFF RECIPIENTS. M.R. Oarovoy, B.W. Colombo, C.D. Lee, L Melzer, N. Aether, L Roberts, WJ.Amend, F. Vincemi, S. Tomlanovich, O. S~dva~erra. lmmunogene~s and T~nsplanmfion Laboratory and Transplant Service, Depm'm~m of Surgery, Urfiver~ty of C.~iforn~, San Francisco. In an attempt to increase the graft survived among sensidzed ImtienLs,we ~Mp~ed a stringent protocol applying prospeedve flow cytome~'y (FCXM), an#globulin and B cell (37°C) crossmatching utilizing current as well as historical ~ = . From 1987 through 1990 patients crossmatch negative by all three criteria were given highest priority. Graft survival has been 84% for 635 prhnary and 84% for 57 regmft patients under this protocol. This ate of graft survive/was ~¢¢n in Im~cms with PRA of 2040%, 40-80% and 8,9-100%. Included in these data are II prima~ and 12 regraft recipients with 80 to 100% PRA. Several interesting crossmatch patterns emerged. There were 65 (29%) positive FCXM out of 223 cyto~oxicity ~gafive crossm~tches primary graft and 41 (39%) positive FCXM out of 104 eyto~oxicity negative crossmatches in regraft recipients. Flow detected the presence of anti-Class I IgG antibody in 53/100 (53%) B-warm positive crossmme~s in pfinml'y grdt and in 59/96 (61%) in regraft recipients. The FCXM was negative among 9/79 (11%) of T ceil positive crossmatehes, suggesting the pre~nee ofIgM anti-HLA antibody. These data suggest that the use of a concurrent batte~ of sensitive crossnmteh techniques may contribute to improved antibody definition and graft survival for high risk pmiems in a large single center transplant experience.

NCOI RESTRICTION FRACaEMT LENGTH P O L Y M O R ~ I S M O F T H E TUMOb~ N~CROSIS FACTOR REGION IN SYSTEMIC LUPUS F/%YEHEMATOSUS. ~ . Ottawa General Hospital, University of Ottawa, Ottawa, Ontario. The human and nurlne tumour necrosis factor (TNF) loci are located between the HLA class Ill and I loci and code for eytekines with nultlple biologic roles, ineludlng host defense against tumour and infection, as well as inflammation and imunity. The TNF locus has been suggested as a possible HL%-linkedgeneinvolved in susceptibility to SLY. In nice, a TNF= RFLP correlates with reduced levels of serum TNF= in NZW autoiL-~une nice, with replacement of TNF= retarding development of nephrltis (Nature 331;356,1988). In humans, TNF= nay be decreased in HLA-D~2 haplotypes and underlie the association of DR2 with systemic lupus er>thematosus (SLE). Preliminary study suggests an increase in a 5.5 kb ~Lql TNFa RFLP in small numbers of patients w i t h S L E a n d several other autoimmune diseases (Tissue Age 34:17,1989), whioh may or may not be secondary to HLA-B8 associations. In this study, 90 Caucasian SLE patients and 79 Caucasian controls had ~9_ql TNF~ RFLPs analyzed. The frequencies of RFLPphenotypes and genotypes for the N~9.ql TNF~ 10.5 and 5.5 kb bands were net dlfferen= in SLE patients versus controls. When the patients were broken down into French-Canadian (FC) and non-FG ethnic groups there was slnilarly no difference in this RFLPeompared to ethnically matched controls. This was true particularly in the largely Anglo-Saxon non-FC SLE group, which we and others have previeuslyshownte have a strong association withHLA-BS, DR3 and CdAgene deletion. These data d o n u t suggest any genetic association of SLE with the .~L~I TNF~ RFLP, either with or without the extended HLA-BS,DR3,CdA~QOhaploL~)T.e-