CYTOKINE GENE POLYMORPHISMS IN UMBILICAL CORD AND ADULT BLOOD-INCREASED IL-6 PRODUCTION GENOTYPE IN UCB.
D. Skerrett, D. Bernstein, C. Swenson, O. Gudzowaty,⁺ C. Zheng,⁺ O.Rosina ⁺Department of Pathology, Columbia University-NY Presbyterian Hospital and ⁺ Tissue Typing Laboratory, Mount Sinai Medical Center, New York, New York.

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Cytokine production by alloreactive lymphocytes is associated with graft versus host disease (GVHD) in stem cell transplants and rejection episodes in solid organ transplants. Umbilical cord blood (UCB) transplants are associated with a decreased incidence of GVHD. We compared cytokine gene polymorphisms in UCB and adult blood to determine whether the reported decreased production of IL-10, IFN-g , TNF-a and TGF-b in stimulated UCB lymphocytes is due to altered regulation of cytokine production.

Cytokine gene expression was determined by assay of the regulatory promoter sequences (SSP, One Lambda, Canoga Park, CA). Samples were analyzed for HLA class I and II alleles to determine the frequency of alleles in each group and to investigate cytokine and HLA haplotype linkage (DNA-SSP and SSOP).

The high TNF-a genotype was significantly decreased in UCB and the IL-6 high production genotype was significantly increased in UCB. The increased frequency of high TNF-a genotype in adult blood was associated with the frequency of HLA*B8, Cw7 and DR3 in the adult group. These HLA antigens are consistent with the known high TNF-a ancestral haplotype, HLA-A1, B8, DR3. Chi-square p values are shown.

Cytokine Gene Polymorphism Frequencies in UCB (N=101) and Adult Blood (N=52)

%High TNF-a TGF-b IL-10 IL-6 IFN-g

Cord 19.8 65.3 12.9 93.1 13.9

Adult 34.6 73.1 17.3 82.7 19.2

p <0.05 <0.05

Cytokine gene polymorphisms in UCB and adult blood were determined. An increased frequency of high IL-6 genotypes was observed in UCB. This finding may be of significance in understanding immunological and hematopoietic responses in UCB.