Villarreal G M, Alarcón-Segovia D, Villa A R, Cabral A R, Shoenfeld Y
Department of Immunology and Rheumatology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City, Mexico.
J Rheumatol. 1991 Oct;18(10):1537-41.
Patients with primary antiphospholipid syndrome (PAPS) have few or no autoantibodies, other than the antiphospholipid antibodies (aPL) that could be natural autoantibodies encoded by germline genes. Some of the autoantibodies marked by the human anti-DNA common idiotype 16/6 have been found to be encoded by unmutated germline genes. Hence, we tested the sera of 19 patients with PAPS for the presence of the 16/6 idiotype which has also been found to be expressed on antibodies that bind cardiolipin. For this we used an ELISA method with antiserum against the SA1 idiotype which recognizes the 16/6. Five of our patients had the idiotype in at least one serum. Among the patients there was one with a variant of PAPS with hemolytic anemia and an IgM antibody to phosphatidylcholine that is akin to the natural autoantibody of normal mice encoded by germline genes VH11 and VH12. Inhibition studies with ssDNA, dsDNA and cardiolipin revealed that all 3 antigens decreased the serum levels of the SA1 idiotype despite absence of detectable anti-DNA antibodies by other methods. Our findings suggest that within the B cell clones that produce aPL in patients with PAPS there are some that produce immunoglobulins bearing 16/6 related idiotypes. This could indicate that some of the aPL present in patients with PAPS derive from natural autoantibody producing cell clones.
原发性抗磷脂综合征(PAPS)患者除了抗磷脂抗体(aPL)外,几乎没有或没有自身抗体,而这些抗磷脂抗体可能是由种系基因编码的天然自身抗体。已发现一些以人抗DNA共同独特型16/6标记的自身抗体是由未突变的种系基因编码的。因此,我们检测了19例PAPS患者血清中是否存在16/6独特型,该独特型也已在与心磷脂结合的抗体上表达。为此,我们使用了一种酶联免疫吸附测定(ELISA)方法,用识别16/6的抗SA1独特型抗血清进行检测。我们的5例患者至少在一份血清中存在该独特型。在这些患者中,有1例患有PAPS变异型,伴有溶血性贫血,且有一种针对磷脂酰胆碱的IgM抗体,类似于由种系基因VH11和VH12编码的正常小鼠的天然自身抗体。用单链DNA、双链DNA和心磷脂进行的抑制研究表明,尽管用其他方法未检测到抗DNA抗体,但所有这3种抗原均降低了SA1独特型的血清水平。我们的研究结果表明,在PAPS患者中产生aPL的B细胞克隆内,有一些克隆产生带有16/6相关独特型的免疫球蛋白。这可能表明,PAPS患者体内存在的一些aPL源自产生天然自身抗体的细胞克隆。