Male-only Systemic Lupus

Abstract

Systemic lupus erythematosus (SLE) is more common among women than men with a ratio of about 10 to 1. We undertook this study to describe familial male SLE within a large cohort of familial SLE. SLE families (two or more patients) were obtained from the Lupus Multiplex Registry and Repository. Genomic DNA and blood samples were obtained using standard methods. Autoantibodies were determined by multiple methods. Medical records were abstracted for SLE clinical data. Fluorescent in situ hybridization (FISH) was performed with X and Y centromere specific probes, and a probe specific for the toll-like receptor 7 gene on the X chromosome. Among 523 SLE families, we found five families in which all the SLE patients were male. FISH found no yaa gene equivalent in these families. SLE-unaffected primary female relatives from the five families with only-male SLE patients had a statistically increased rate of positive ANA compared to SLE-unaffected female relatives in other families. White men with SLE were 5 times more likely to have an offspring with SLE than were White women with SLE but there was no difference in this likelihood among Black men. These data suggest genetic susceptibility factors that act only in men.

Parental history of lupus and rheumatoid arthritis and risk in offspring in a nationwide cohort study: does sex matter?

“…This led the authors to infer that men were overrepresented as parents of offspring with SLE 37. However, because that study was composed of families with at least two SLE cases rather than being population based, it may have been subject to selection biases, such as the inclusion of cases with greater genetic risk or disease severity, or a greater tendency for men with affected offspring to participate due to the rarity of SLE in men.…”

Autoimmune disease and gender: Plausible mechanisms for the female predominance of autoimmunity

“…Not only do women and men differ in their normal immune response but there are also differences between them in the prevalence, presentation and severity of ADs. This leads to the notion that increased immune function imparts increased susceptibility to autoimmunity in women [2,18,84,85]. There are multiple hypotheses about the genetic mechanisms that could explain the sex bias in ADs.…”

Lupus After Kidney Donation to an Affected Male Relative

“…Among families in which at least one SLE patient was a woman, only 19 of 48 (40%) female first-degree relatives had a positive ANA (p = 0.0006 compared to the relatives in the families with all male SLE) (15). Our patient’s persistent ANA negativity and anti-dsDNA positivity is atypical of what has previously been reported in this context.…”

“…In addition, these same authors showed that the prevalence of renal disease (with or without a formal diagnosis of SLE using American College of Rheumatology diagnostic criteria) is significantly increased in female family members of men with SLE as compared to women with an affected female relative (68% versus 43%; P = 0.002). Subsequent studies suggest that for families with only affected male relatives, the etiology of SLE occurrence likely relates to a relatively greater genetic predisposition than is present in families with familial SLE but no (or relatively fewer) affected males (15). Although not studied directly, based on the current evidence and highlighted by our case, it can be inferred that the future risks of developing SLE and LN may be especially elevated for potential kidney donors who are first-degree relatives of SLE-affected men.…”