Background/Purpose:   IgG4-related disease (IgG4-RD) is a multi-organ affecting disease characterized by fibroinflammatory lesions with a abundant IgG4-positive plasma cells infiltration. This disorder includes many conditions such as autoimmune pancreatitis, Mikulicz disease and retroperitoneal fibrosis. Elevation of serum IgG4 levels is frequently found and is a key clue for diagnosis of IgG4-RD. However, there are patents who do not have fibrotic-sclerotic lesions, characteristics of IgG4-RD, but revealed elevation of serum IgG4. To determine whether IgG4-RD is a distinct subtype of diseases with hyper-IgG4, we conducted cluster analysis of patients with elevation of serum IgG4 levels and examined clinical features of each cluster.

Methods: Subjects were 86 patients with elevation of serum IgG4 (>100mg/dl) among 350 patients whom received IgG4 examination for diagnosis of mass lesions or inflammation. Cluster analysis of organ involvements of the patients were performed through Ward’s method. Clinical features of patients in each cluster were e4xamined through reviewing medical records retrospectively.

Results: Through cluster analysis, 5 clusters were identified: cluster1; patients with multiple organ involvements including salivary glands, eyes, pancreas and retroperitoneum (typical IgG4 RD), cluster 2; patients with autoimmene pancreatitis alone (a subset of IgG4-RD), cluster 3; patients with lung involvement alone, cluster 4; patients with pleuritis alone, and cluster 5; patients without specific organ involvements. Renal involvement was found in patients in cluster1; generalized lymphadenopathy was detected in those in cluster 1, and pulmonary involvement was seen in those in cluster 1. Serum IgG4 level were significantly high in patients in cluster 1 compared to those in other clusters. In addition, serum IgG4 levels were increased in correlation with numbers of affected organs in cluster 1. Hypergammaglobulinemia occurred frequently in cluster 1. Serum CRP elevation was not found in cluster 1 and 2. IgG4 plasma cell rich infiltration was found in some biopsy samples from patients in all clusters. Glucocorticoid was effective on inflammatory lesions and systemic inflammation in most cases of all clusters.

Conclusion: Typical IgG4-RD (cluster1) is a distinct subtype of diseases with serum IgG4 elevation, which is characterized by multiple organ involvements, particularly salivary glands, eyes and retroperitoneum, generalize lymphadenopathy, marked IgG4 elevation with hypergammaglobulinemia and absence of systemic inflammation.

---

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/cluster-analysis-of-organ-involvements-patients-with-serum-igg4-elevation-igg4-related-disease-is-a-distinct-subtype-of-patients-with-hyper-igg4/