Danieli Maria Giovanna, Mezzanotte Cristina, Paladini Alberto, Benfaremo Devis, Murdaca Giuseppe, Moroncini Gianluca
Immunology of Rare Diseases and Transplants, Department of Internal Medicine, Marche University Hospital, Ancona, Italy.
Postgraduate School of Allergy and Clinical Immunology, Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy.
J Scleroderma Relat Disord. 2025 May 4:23971983251333851. doi: 10.1177/23971983251333851.
Hypogammaglobulinemia is a condition that can be related to both primary and secondary immunodeficiencies. While the role of primary immunodeficiency in immune-mediated diseases is well known, its occurrence in systemic sclerosis is not reported.
This study aims to describe the clinical features associated with hypogammaglobulinemia in a cohort of limited cutaneous systemic sclerosis patients.
We retrospectively reviewed medical records of systemic sclerosis patients from two Italian referral centres (2010-2024). Included patients had limited cutaneous systemic sclerosis and presented reduced serum concentrations of one or more Ig isotypes (IgG < 700 mg/dL, IgA < 70 mg/dL or IgM < 50 mg/dL) in at least two separate measurements. Patients with secondary causes of hypogammaglobulinemia were excluded. Data collected included demographics, clinical features, Ig levels, infection history and comorbidities.
We identified 30 systemic sclerosis patients (93% female, mean age 62 years) with limited cutaneous involvement and hypogammaglobulinemia. Most patients were positive for anti-centromere antibodies and received periodic intravenous infusions of prostaglandin analogues. No patient received immunosuppressive therapy. Median (interquartile range) serum IgG levels 519.5 (175) mg/dL, median IgA 65.5 (48) mg/dL and median IgM 71.5 (49) mg/dL. Four patients who met the European Society for Immunodeficiencies (ESID) criteria for common variable immunodeficiency experienced recurrent infections and had associated immune-mediated diseases. Five patients had selective IgA deficiency, with frequent immune-mediated comorbidities (thyroiditis, Sjögren's syndrome, arthritis, psoriasis). The other patients exhibited mild IgG deficiency without a significant infectious history.
This is the first study describing a cohort of patients with limited cutaneous systemic sclerosis and hypogammaglobulinemia. Our population presented a high prevalence of immune-mediated comorbidities but low infection rates. Further research is needed to explore the underlying mechanisms and clinical significance of hypogammaglobulinemia in these patients.
低丙种球蛋白血症是一种可与原发性和继发性免疫缺陷相关的病症。虽然原发性免疫缺陷在免疫介导疾病中的作用已广为人知，但其在系统性硬化症中的发生情况尚未见报道。
本研究旨在描述一组局限性皮肤型系统性硬化症患者中与低丙种球蛋白血症相关的临床特征。
我们回顾性分析了来自两个意大利转诊中心（2010 - 2024年）的系统性硬化症患者的病历。纳入的患者患有局限性皮肤型系统性硬化症，且在至少两次独立测量中出现一种或多种免疫球蛋白亚型的血清浓度降低（IgG < 700 mg/dL、IgA < 70 mg/dL或IgM < 50 mg/dL）。排除低丙种球蛋白血症继发原因的患者。收集的数据包括人口统计学、临床特征、免疫球蛋白水平、感染史和合并症。
我们确定了30例患有局限性皮肤受累和低丙种球蛋白血症的系统性硬化症患者（93%为女性，平均年龄62岁）。大多数患者抗着丝点抗体呈阳性，并接受周期性静脉输注前列腺素类似物。无患者接受免疫抑制治疗。血清IgG水平中位数（四分位间距）为519.5（175）mg/dL，IgA中位数为65.5（48）mg/dL，IgM中位数为71.5（49）mg/dL。4例符合欧洲免疫缺陷学会（ESID）常见变异型免疫缺陷标准的患者经历了反复感染，并患有相关的免疫介导疾病。5例患者患有选择性IgA缺乏症，伴有频繁的免疫介导合并症（甲状腺炎、干燥综合征、关节炎、银屑病）。其他患者表现为轻度IgG缺乏，无明显感染史。
这是第一项描述一组局限性皮肤型系统性硬化症和低丙种球蛋白血症患者的研究。我们的研究人群中免疫介导合并症的患病率高，但感染率低。需要进一步研究以探索这些患者低丙种球蛋白血症的潜在机制和临床意义。
