Pediatric Clinical Immunology and Allergology Service at the Hospital de Pediatria, Centro Medico Nacional de Occidente, IMSS, Guadalajara, Jalisco, Mexico.
Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Clin Immunol. 2024 Sep;266:110335. doi: 10.1016/j.clim.2024.110335. Epub 2024 Aug 3.
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.
在成年人中更为常见，表型可能由体细胞突变或抗细胞因子自身抗体引起，模拟原发性免疫缺陷的表型。一名 14 岁女孩因两年体重减轻和多次复发性脓肿、反复肺炎、肾盂肾炎、骨髓炎和感染性休克而就诊，无发热。她开始出现恶心、食欲不振和体重减轻，随后手部、膝盖、脚踝和脾脏出现脓肿。她还出现了肋骨骨折和左侧胸带状疱疹。患者消瘦，生命体征正常，胸部听诊有双侧爆裂音，膝关节肿胀，手部和胸部伤口愈合不良，渗出淡黄色液体。胸部计算机断层扫描显示多发双侧支气管扩张。实验室检查报告慢性贫血、白细胞增多、中性粒细胞增多、轻度淋巴细胞减少、血小板增多、全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。在踝关节骨髓炎的骨活检标本中通过聚合酶链反应检测到结核分枝杆菌。全外显子组测序未发现单基因缺陷。患者血清中白细胞介素-12 明显升高。随着白细胞介素-12 剂量的增加，STAT4 的磷酸化被患者血清中和，证实存在抗白细胞介素 12 自身抗体。白细胞介素-12 和白细胞介素-23 是对抗细胞内微生物、诱导淋巴细胞产生干扰素-γ和其他炎症功能的关键细胞因子。产生针对白细胞介素 12 的中和血清自身抗体的患者在晚年出现体重减轻、多发复发性脓肿、伤口愈合不良和瘘管。抗 CD20 单克隆抗体治疗有效。
