Statement of Purpose. IgG4-related disease (IgG4-RD) is usually associated to an increase of serum IgG4 levels. However other conditions have also been associated to high serum IgG4 levels. Methods. All IgG subclasses analyses performed in our hospital over a one-year period were analyzed. When IgG4 level were over 1.35？g/L, the patient’s clinical observation was analyzed and both final diagnosis and reason leading to IgG subclasses analysis were recorded. Only polyclonal increases of IgG4 were considered. Summary of the Results. On 646 IgG subclass analysis performed, 59 patients had serum IgG4 over 1.35？g/L. The final diagnosis associated to serum IgG4 increase was very variable. Most patients (25%) presented with repeated infections, 13.5% with autoimmune diseases, and 10% with IgG4-RD. Other patients presented with cancer, primary immune deficiencies, idiopathic interstitial lung disease, cystic fibrosis, histiocytosis, or systemic vasculitis and 13.5% presented with various pathologies or no diagnosis. Mean IgG4 levels and IgG4/IgG ratio were higher in IgG4-RD than in other pathologies associated to elevated IgG4 levels. Conclusions. Our study confirms that elevation of serum IgG4 is not specific to IgG4-RD. Before retaining IgG4-RD diagnosis in cases of serum IgG4 above 1.35？g/L, several other pathological conditions should be excluded. 1. Introduction Immunoglobulin G4 (IgG4) represents the less abundant of the four IgG subclasses in human serum accounting for 3 to 6% of the total IgG [1]. IgG4 has been associated with several pathological conditions. Most of these associations suggest a protective effect of IgG4, such as in allergen-specific immunotherapy [2] and protection from inflammatory manifestations during parasitosis [3]. In few situations, IgG4 is associated with a direct pathogenic effect, such as in pemphigus. During this blistering dermatosis, antidesmosome autoantibodies belong to the IgG4 subclass [4]. However, total IgG4 serum levels are not raised in these conditions. In 2001, Hamano et al. report a quantitative serum IgG4 elevation during sclerosing (or “autoimmune”) pancreatitis above the cutoff value of 135？mg/dL in 95% of patients with autoimmune pancreatitis [1]. This entity was first described in 1961 by Sarles and colleagues in patients with lymphoplasmacytic infiltrate and fibrosis of the pancreas associated to polyclonal hypergammaglobulinemia [5]. Polyclonal hypergammaglobulinemia raised initially the issue of the possible auto-immune nature of the disease, but this hypothesis has not been confirmed to date. Indeed, no
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