Background/Purpose:

Anti-β₂glycoprotein I antibodies (a-β₂GPI) are involved in the pathogenesis of the Antiphospholipid Syndrome (APS). Antibodies to the domain 1 of β₂GP1 (a-β₂GPI-D1) have been suggested as a marker of thrombosis, while antibodies to domain 4/5 (a-β₂GPI-D4/5) have been described in non-thrombotic, non-autoimmune conditions. The clinical significance of these biomarkers is still evolving. We analyze different groups of patients affected by systemic autoimmune diseases and asymptomatic carriers of anti-phospholipid antibodies (aPL).

Methods:

154 patients with positive IgG a-β₂GPI at routine assay were enrolled in this multicenter study: A) 55 thrombotic (+/- obstetric) primary APS (PAPS); B) 31 women with pure obstetric PAPS; C) 42 Systemic Lupus Erythematosus (SLE)/Undifferentiated Connective Tissue Disease (UCTD) with positive aPL but without any APS event in their medical history; D) 14 asymptomatic aPL carriers; E) 12 Rheumatoid Arthritis (RA). As controls, 99 adult normal healthy donors (NHD) were included. IgG a-β₂GPI-D1 and IgG a-β₂GPI-D4/5 were tested on research ELISAs containing recombinant β2GPI domain antigens. The results were considered as optical density (OD) values.

Results:

Table shows median OD values in each group. To define the preferential specificity of a-β₂GPI, the ratio between a-β₂GPI-D1 and a-β₂GPI-D4/5 was calculated. A p value less than 0.05 was considered as significant (ns=not significant).

	IgG a-β2GPI (routine assay)	IgG a-β2GPI-D1	IgG a-β2GPI-D4/5	Mann-Whitney Test a-D1 vs a-D4/5	D1 – D4/5 RATIO (median)
Thrombotic PAPS (n=55)	1.324	0.458	0.171	p<0.0001	2.3
Obstetric PAPS (n=31)	1.058	0.312	0.154	p=0.0003	2.4
SLE/UCTD with aPL (n=42)	0.953	0.497	0.204	p<0.0001	2.1
aPL carriers (n=14)	1.030	0.317	0.228	p=ns	1.2
RA (n=12)	0.917	0.202	0.519	p=ns	1.0
NHD (n=99)	0.041	0.109	0.080	p=ns	1.4

Conclusion:

A-β₂GPI-D1 is the prevalent specificity of a-β₂GPI not only in PAPS with thrombosis, but also in PAPS with pure obstetric disease and in SLE/UCTD patients with no APS manifestations. In the latter group, the pathogenic potential of a-β₂GPI-D1 might be mitigated by the absence of additional risk factors and/or to the presence of adequate prophylaxis. aPL carriers appear not to have a polarized profile, suggesting that a-β₂GPI-D1 may be a fingerprint of systemic autoimmune diseases.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/domain-1-is-the-main-specificity-of-anti-%ce%b22glycoprotein-i-antibodies-in-systemic-autoimmune-diseases/