Abstract：
More frequent among adults, phenocopies may be caused by somatic mutations or anti-cytokine autoantibodies, mimicking the phenotypes of primary immunodeficiencies. A fourteen-year-old girl was referred for a two-year history of weight loss and multiple recurrent abscesses, complicated recurrent pneumonia, pyelonephritis, osteomyelitis, and septic shock, without fever. She had started with nausea, hyporexia, and weight loss, then with abscesses in her hands, knee, ankle, and spleen. She also developed a rib fracture and left thoracic herpes zoster. The patient was cachectic, with normal vital signs, bilateral crackles on chest auscultation, tumefaction of the knee joint, and poorly healed wounds in hands and chest, oozing a yellowish fluid. Chest computed tomography revealed multiple bilateral bronchiectases. Laboratory workup reported chronic anemia, leukocytosis, neutrophilia, mild lymphopenia, thrombocytosis, pan-hypergammaglobulinemia, and elevated acute serum reactants. Lymphocyte subsets were low but present. Mycobacterium tuberculosis was detected via polymerase chain reaction in a bone biopsy specimen from ankle osteomyelitis. Whole-exome sequencing failed to identify a monogenic defect. Interleukin-12 was found markedly elevated in the serum of the patient. Phosphorylation of STAT4, induced by increasing doses of IL-12, was neutralized by patient serum, confirming the presence of anti-IL12 autoantibodies. IL-12 and IL-23 are crucial cytokines in the defense against intracellular microorganisms, the induction of interferon-gamma production by lymphocytes, and other inflammatory functions. Patients who develop neutralizing serum autoantibodies against IL12 manifest late in life with weight loss, multiple recurrent abscesses, poor wound healing, and fistulae. Treatment with anti-CD20 monoclonal antibodies was effective.
摘要：
在成年人中更常见，表型可能由体细胞突变或抗细胞因子自身抗体引起，模仿原发性免疫缺陷的表型。一名十四岁女孩因两年的体重减轻和多发性复发性脓肿病史而被转诊，复杂的复发性肺炎，肾盂肾炎,骨髓炎,和感染性休克,没有发烧。她开始恶心，缺氧,和减肥,然后她手上有脓肿,膝盖,脚踝,还有脾脏.她还出现了肋骨骨折和左胸带状疱疹。病人有恶病质,生命体征正常,胸部听诊时双侧有裂纹，膝关节的肌动,手和胸部的伤口愈合不良，渗出淡黄色液体。胸部计算机断层扫描显示双侧多个支气管扩张。实验室检查报告慢性贫血,白细胞增多,嗜中性粒细胞增多症,轻度淋巴细胞减少,血小板增多症,泛-高丙种球蛋白血症,和急性血清反应物升高。淋巴细胞亚群较低，但存在。通过聚合酶链反应在踝关节骨髓炎的骨活检标本中检测到结核分枝杆菌。全外显子组测序未能鉴定出单基因缺陷。在患者血清中发现白细胞介素-12显著升高。通过增加IL-12剂量诱导的STAT4的磷酸化被患者血清中和，确认抗IL12自身抗体的存在。IL-12和IL-23是防御细胞内微生物的关键细胞因子，诱导淋巴细胞产生干扰素-γ，和其他炎症功能。产生针对IL12的中和血清自身抗体的患者在体重减轻的晚期表现，多发性复发性脓肿,伤口愈合不良,还有瘘管.用抗CD20单克隆抗体治疗是有效的。
