血清性抗リン脂質症候群の診断におけるアネキシンA5抵抗性と非基準抗体の意義

Annexin-A5 resistance and non-criteria antibodies for the diagnosis of seronegative antiphospholipid syndrome.

• Théo Ghelfenstein Ferreira
• François Delhommeau
• Catherine Johanet
• Grigorios Gerotziafas
• Marie Bornes
• Jonathan Cohen
• Gilles Kayem
• Olivier Fain
• Virginie Planche
• Arsene Mékinian

抄録

本研究では，臨床的セロネガティブ抗リン脂質症候群患者のAPS診断におけるアネキシンA5抗凝固比（A5R）と非基準抗体の値を解析することを目的とした．原因不明の産科有害事象や血栓症の既往のある血清陰性APS患者21例、トリプルaPL陽性の確定APS患者15例、血栓症や妊娠合併症の既往のない健康な患者20例の対照群の3群を定義した。血清陰性APS患者は健常対照群と比較して同程度のA5R値を示した（202％［171％-238％］対191％［178％-221％］；p＝0.65）一方、トリプル陽性APS患者は、血清陰性患者および健常患者の両方と比較して有意にA5R値が低下していた（149％［138％-158％］対202％［171％-238％］対191％［178％-221％］、それぞれp＜0.001）。非基準APLは血清陰性APSの24％に認められた：抗PE IgMは3例（14％）、抗PS/PT IgGおよび抗PS/PT IgMは各1例（5％）に認められた。非基準APLの頻度は健常対照と比較して有意に高かった（p=0.048）。すべてのトリプル陽性APS患者は少なくとも1つの非基準APLを有しており、これらの患者では、血清陰性APSおよび健常対照群と比較して非基準APLの頻度が有意に高かった（p＜0.001）。本研究では，A5Rレベルでは血清陰性APSと健常者を区別できないが，非基準抗リン脂質抗体が血清陰性APSの診断に有用であることを明らかにした．

In this study, we aimed to analyze the value of annexin-A5 anticoagulant ratio (A5R) and non-criteria antibodies for the diagnosis of APS in patients with clinical seronegative APS. Three groups were defined, including 21 seronegative APS patients with unexplained obstetrical adverse events or thrombosis history, 15 confirmed APS patients with triple aPL positivity, and a control group of 20 healthy patients without any history of thrombosis or pregnancy complications. Seronegative APS patients have similar levels of A5R in comparison to healthy controls (202% [171%-238%] versus 191% [178%-221%]; p = 0.65), whereas triple-positive APS patients have significantly more reduced A5R in comparison to both seronegative and healthy patients (149% [138%-158%] versus 202% [171%-238%] and 191% [178%-221%], respectively, p < 0.001). The non-criteria aPL were found in 24% of seronegative APS: anti-PE IgM in 3 cases (14%) and anti-PS/PT IgG and anti-PS/PT IgM in 1 (5%) case each. The frequency of non-criteria APL was significantly more frequent in comparison to healthy controls (p = 0.048). All triple-positive APS patients have at least one non-criteria aPL, and the non-criteria aPL were significantly more frequent in these patients compared to seronegative APS and healthy controls (p < 0.001). Whereas A5R levels do not allow to discriminate seronegative APS from healthy controls, our results demonstrate that non-criteria aPL can help to APS diagnosis in clinical seronegative APS.Key points• Annexin-A5 resistance testing does not help for the diagnosis of seronegative APS.• The non-criteria antiphospholipid antibodies can contribute to APS diagnosis in patients without conventional antibodies.