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Enhanced in vitro IgM rheumatoid factor synthesis in seropositive rheumatoid arthritis families
Abstract:
We studied the patterns of in vitro IgM RF production by peripheral blood mononuclear leukocytes (MNL) in first- and second-degree relatives and non-blood relatives of 14 RA patients. In all these included 25 individuals with RA (14 probands, 11 other affected members), 88 non-affected first- and second-degree relatives and 15 non-affected non-blood relatives. In vitro production of IgM RF and IgM by MNL from RA patients was similar to what we and others have previously described. Spontaneous production of IgM RF was demonstrated by MNL from some RA patients and the ratio of IgM RF to total IgM was higher for patients than controls. The non-blood relatives failed to demonstrate spontaneous in vitro IgM RF production. In contrast, MNL from approximately 16% of non-affected blood relatives spontaneously produced IgM RF. Spontaneous IgM RF production in this group did not correlate with HLA-DR3 or HLA-DR4 and was found in Caucasoids. American blacks, simplex (one affected individual), and multiplex (more than one affected individual) families. Linkage analysis using either a recessive or dominant model of inheritance failed to detect linkage among affected and non-affected family members.
Insights
Rheumatoid arthritis (RA) patients show higher IgM rheumatoid factor (RF) production. Some unaffected relatives also produce IgM RF, but this doesn't link to genetics, suggesting environmental factors may play a role.
Area of Science:
- Immunology
- Genetics
- Rheumatology
Background:
- Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation.
- Immunoglobulin M rheumatoid factor (IgM RF) is a common autoantibody found in RA patients.
- The genetic and environmental factors contributing to RA pathogenesis are not fully understood.
Purpose of the Study:
- To investigate in vitro IgM RF production in individuals with RA and their relatives.
- To explore potential genetic linkages associated with IgM RF production in RA families.
- To differentiate between genetic and potential environmental influences on IgM RF expression.
Main Methods:
- Peripheral blood mononuclear leukocytes (MNL) were isolated from RA patients, affected relatives, unaffected blood relatives, and non-blood relatives.
- In vitro production of IgM RF and total IgM by MNL was measured.
- Linkage analysis was performed using both recessive and dominant inheritance models.
Main Results:
- MNL from RA patients exhibited similar in vitro IgM RF production compared to previous studies, with a higher IgM RF to IgM ratio.
- Non-blood relatives did not produce spontaneous IgM RF.
- Approximately 16% of unaffected blood relatives showed spontaneous IgM RF production, independent of HLA-DR3/DR4 status, ethnicity, or family structure (simplex/multiplex).
- Linkage analysis failed to detect a significant genetic linkage for IgM RF production.
Conclusions:
- Spontaneous IgM RF production occurs in a subset of unaffected relatives of RA patients.
- The absence of genetic linkage suggests that factors other than simple Mendelian inheritance influence IgM RF production in RA families.
- Environmental factors may play a significant role in the expression of IgM RF in individuals predisposed to or affected by RA.