A genetic glitch in one inhibitory receptor (FcγRIIB) stops it from working properly, so the immune system can’t calm down — leading to attacks on the body’s own tissues.
Scientific Claim
The FcγRIIB T232 polymorphism impairs inhibitory function by disrupting lipid raft localization and SHIP recruitment, leading to unchecked activating FcγR signaling and increased autoantibody production.
Original Statement
“The polymorphism, 695T > C, resulted in a non-synonymous substitution, Ile232Thr (I232T), within the transmembrane domain of FcγRIIB. ... FcγRIIBT232 resulted in paradoxical de-phosphorylation, altered phosphatase interaction, and phosphorylation independent recruitment of SHIP. ... only wt FcγRIIB, but not FcγRIIBT232, was readily detectable in the lipid raft fraction of U937 cells. ... Humanized mice with this mutation produced higher levels of serum IgM and IgG ... and began to produce autoantibodies directed against double-stranded DNA ... typical for SLE patients.”
Evidence Quality Assessment
Claim Status
appropriately stated
Study Design Support
Design supports claim
Appropriate Language Strength
definitive
Can make definitive causal claims
Assessment Explanation
The claim describes a well-characterized molecular mechanism from multiple primary studies using cell lines, transgenic mice, and biochemical assays. Definitive language is justified by the depth of mechanistic evidence.
Evidence from Studies
Supporting (0)
Contradicting (1)
This study talks generally about how certain immune receptors work in diseases like lupus, but it doesn’t mention the specific genetic change (T232) or how it breaks the immune system’s brakes, so we can’t say if the claim is right or wrong based on this paper.