ArticleClinical rheumatology2026
Elevated serum IgG1, complement activation, and clinical severity in IgG4-related disease: a comprehensive subgroup analysis.
Article in Clinical rheumatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introduction
objectivesTo evaluate the clinical associations of elevated serum IgG1 and to assess the utility of integrating IgG1 with IgG4 for patient stratification in IgG4-related disease (IgG4-RD).
methodThis retrospective study included 344 treatment-naïve IgG4-RD patients. Patients were first classified into elevated and non-elevated IgG1 groups based on the institutional laboratory upper limit of normal (ULN) (cutoff: 10.11 g/L). Subsequently, to explore distinct immunopathological phenotypes, patients were further stratified into four groups by integrating this IgG1 cutoff with an IgG1/IgG4 ratio cutoff of 1.0. Subgroup analyses were performed based on gender and the presence of lung, kidney, or liver involvement.
resultsPatients with elevated IgG1 (> 10.11 g/L, n = 137) were older, more frequently male, and had higher disease activity, more organ involvement, and increased lung, kidney, and liver involvement (all P < 0.05). They exhibited profound hypocomplementemia, with serum IgG1 levels showing strong negative correlations with both C3 (r = -0.43, P < 0.001) and C4 (r = -0.48, P < 0.001). Crucially, the most severe phenotype was defined by the "Elevated IgG1, non-IgG1-dominant" signature (IgG1 > 10.11 g/L and IgG1/IgG4 < 1.0). Subgroup analyses revealed exceptionally strong IgG1-complement correlations in males and in patients with kidney or liver involvement.
conclusionsElevated serum IgG1 marks a severe IgG4-RD phenotype. The "Elevated IgG1, non-IgG1-dominant" serological signature specifically identifies a more severe phenotype, characterized by complement consumption and multi-organ injury. This composite marker may serve as a useful tool for risk stratification. Keypoints • Elevated serum IgG1 (>10.11 g/L) defines a severe IgG4-RD phenotype with higher disease activity, multi-organ involvement, and profound complement consumption. • A novel serological signature, "Elevated IgG1, non-IgG1-dominant" (IgG1>10.11 g/L and IgG1/IgG 4<1.0), identifies a more severe phenotype of IgG4-RD patients. • Serum IgG1 correlates strongly with hypocomplementemia, with exceptionally strong correlations in male patients and those with kidney or liver involvement.
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