Lymphocytes and rheumatoid arthritis

Mandeville, Robert Parnell (1978) Lymphocytes and rheumatoid arthritis. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

This thesis describes research into the immunological aspects of Rheumatoid Arthritis. The work uses as its model the immune-mediated reactions between graft and host which have been investigated intensively by immunologists in animals. The only natural situation in which these reactions might be precipitated are those that arise during pregnancy when the immune systems of mother and offspring are in close contiguity. Accordingly pregnancy is the focal point with concentration upon aetiological agents that might interact with the genetic make-up of mother and child to give rise to the disease manifestation of Rheumatoid Arthritis in the later life of the offspring. -- In order to see if specific immunological sensitivity or tolerance could be passed from mother to offspring experiments were performed on rats in which the skin sensitizing agent Dinitrochlorobenzene was put on females prior to mating and the offspring were tested for hypersensitivity using a popliteal lymph node weight assay. Within the limits of this assay there was no detectable effect of maternal priming on the reaction of the offspring to this antigen. However, there was a pronounced effect of maternal priming on the spleen weights of the offspring in spite of the removal of the antigen in the skin slough by the time of conception. The spleen weights had been determined crudely to detect immunological runting in the offspring but retrospective analysis revealed that in all experiments in which this protocol was followed the spleen effect was significant in spite of the standard error introduced by the assay. -- Five Juvenile Rheumatoid Arthritis families were investigated using the mixed leucocyte culture reactions to detect genetically determined factors that might predispose to maternal-offspring immune interaction. Two and possibly three of the probands were homozygotes at the HLA-D locus and in two of the families there was some evidence of genotypic or phenotypic inter-ference not related to the HLA region of chromosome six. These results are discussed in the light of the initial model and some possible immunological mechanisms outlined in an appendix.

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