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Defective major histocompatibility complex class I expression on lymphoid cells in autoimmunity
Y Fu1, D M Nathan, F Li
1Immunobiology Laboratory, Massachusetts General Hospital, Boston.
The Journal of Clinical Investigation
|May 1, 1993
Summary
Autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM), show reduced major histocompatibility complex (MHC) class I expression on lymphocytes. This finding suggests MHC class I may be crucial for self-tolerance, and its abnormalities could contribute to autoimmunity.
Area of Science:
- Immunology
- Genetics
- Autoimmunity
Background:
- Autoimmune diseases like IDDM are linked to MHC class II genes.
- Previous studies indicated reduced surface MHC class I antigen expression in IDDM lymphocytes.
- The relationship between MHC class II and MHC class I expression warrants further investigation in various autoimmune conditions.
Purpose of the Study:
- To investigate whether MHC class I expression is abnormal in patients with various autoimmune diseases.
- To determine if decreased MHC class I expression is a common feature across different autoimmune conditions.
Main Methods:
- Peripheral blood lymphocytes (PBLs) were isolated from patients with IDDM, Hashimoto's thyroiditis, Graves' disease, systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome.
- Control groups included nondiabetic and non-insulin-dependent diabetes mellitus patients.
- MHC class I expression was quantified using the W6/32 monoclonal antibody.
Main Results:
- PBLs and EBV-transformed B cell lines from patients with autoimmune diseases exhibited decreased MHC class I expression compared to controls.
- Only a small number of individuals without diagnosed autoimmune disease showed persistently low MHC class I expression, with some revealing occult autoimmunity.
- Patients with nonautoimmune inflammation (osteomyelitis, tuberculosis) displayed normal MHC class I levels.
Conclusions:
- Decreased MHC class I expression is a characteristic feature of lymphocytes in autoimmune diseases.
- Abnormalities in MHC class I expression, potentially impacting self-tolerance, may play a role in the development of autoimmunity.