Lazarou Ilias, Petitpierre Nicolas, Auger Isabelle, Reber Guido, Roux-Lombard Pascale, Boehlen Françoise, Villard Jean
a Division of Immunology and Allergology, University Hospitals of Geneva , Switzerland.
Mod Rheumatol. 2015 Sep;25(5):790-3. doi: 10.3109/14397595.2013.844392. Epub 2015 Jul 29.
Rheumatoid arthritis (RA) is a risk factor for the development of Felty's syndrome and large granular lymphocyte (LGL) leukemia. Anti-cyclic citrullinated peptide (CCP) antibodies are considered highly specific for RA and are directed against various citrullinated antigens, including citrullinated fibrinogen. Anti-CCP antibodies may interfere with the detection of citrullinated proteins and their function. In this article, we describe the possible inhibition of fibrinogen by anti-CCP antibodies with clinical consequences which have never been reported in the literature to our best knowledge.
We present the case of a 79-year-old Caucasian woman with a longstanding history of untreated seropositive RA and who had been investigated for severe neutropenia since several months. The association of splenomegaly led to suspicion of Felty's syndrome. Flux cytometry was compatible with T-cell LGL leukemia. In addition, severe hypofibrinogenemia was detected. The later finding has not been consistently associated with the former clinical entities. Further investigations demonstrated that the anti-CCP antibodies of the patient also recognized the P41 peptide of citrullinated fibrinogen. The patient deceased of intracranial hemorrhage.
It is likely, yet not definite, that high anti-citrullinated fibrinogen titers may contribute to low fibrinogen levels and could have contributed to the fatal hemorrhagic event.
类风湿关节炎（RA）是发生费尔蒂综合征和大颗粒淋巴细胞（LGL）白血病的一个危险因素。抗环瓜氨酸肽（CCP）抗体被认为对RA具有高度特异性，且针对包括瓜氨酸化纤维蛋白原在内的各种瓜氨酸化抗原。抗CCP抗体可能会干扰瓜氨酸化蛋白的检测及其功能。在本文中，我们描述了抗CCP抗体对纤维蛋白原可能的抑制作用及其临床后果，据我们所知，这在文献中从未有过报道。
我们报告一例79岁的白种女性患者，有长期未经治疗的血清阳性RA病史，数月来因严重中性粒细胞减少接受检查。脾肿大的关联导致怀疑费尔蒂综合征。流式细胞术与T细胞LGL白血病相符。此外，检测到严重的纤维蛋白原血症。后一发现与先前的临床病症并无一致关联。进一步检查表明，该患者的抗CCP抗体也识别瓜氨酸化纤维蛋白原的P41肽。患者死于颅内出血。
抗瓜氨酸化纤维蛋白原高滴度很可能（但不确定）导致纤维蛋白原水平降低，并可能导致致命的出血事件。
