A case of IgG4-related tubulointerstitial nephritis concurrent with Henoch-Schönlein purpura nephritis
© Tamai et al; licensee BioMed Central Ltd. 2011
Received: 14 January 2011
Accepted: 31 March 2011
Published: 31 March 2011
We describe a 72-year-old man, who had been suffered from Henoch-Schönlein purpura (HSP) several times, presented with hematoproteinuria with granular cast, and general lymphadenopathy. The immunological examination of the serum showed polyclonal hypergammagloburinemia with high value of IgG4. The renal biopsy revealed interstitial inflammatory cell infiltration, including infiltration of lymphocytes and plasma cells, and segmental glomerulonephritis. Direct immunofluorescence microscopy revealed apparent positive staining with anti-human IgA, and anti-human IgG in glomeruli, anti-human IgG4 antibody staining showed many positive plasma cells in the interstitium. The patient was diagnosed with HSP nephritis that was complicated by IgG4-related nephropathy. As a result of the treatment with 30mg prednisolone, the swelling of the LNs decreased, but the patient continued to have persistent hematoproteinuria.
A novel clinicopathological entity of IgG4-related autoimmune disease characterized by extensive IgG4-positive plasma cell infiltration of organs together with CD4- or CD8-positive T lymphocytes is proposed . Renal involvement in this entity was also suggested, and three patterns of renal involvement have been described: 1) extraparenchymal involvement such as hydronephrosis associated with retroperitoneal lesions; 2) diffuse tubulointerstitial nephritis (TIN); and 3) renal lesions composed of focal lymphoplasmacytic infiltration of the renal interstitium . In this report we describe a rare case diagnosed with HSP nephritis that was complicated by IgG4-related nephropathy.
The patient was diagnosed with HSP nephritis that was complicated by IgG4-related TIN. The patient was treated with PSL (30 mg/day) for 14 days, followed by tapering of PSL. As a result of the treatment, the swelling of the LNs decreased, but the patient continued to have persistent hematoproteinuria.
HSP has been recognized as a distinct clinical condition. The syndrome is also referred to as anaphylactoid purpura and allergic purpura because of circumstantial evidence implicating hypersensitivity to bacteria or viruses as a possible cause. Histopathological examinations revealed that the cutaneous lesions result from leukocytoclastic vasculitis. Immunofluorescence studies have revealed immunoglobulin (Ig) and complement component deposits in the cutaneous blood vessels and kidney, but serum complement levels are usually normal. IgA is the most abundant and sometimes the only Ig found in the skin and kidney lesions. The morphologic and immunopathologic features are similar in HSP nephritis and IgA nephropathy (IgAN), which is characterized by various degrees of focal or diffuse mesangial proliferation, diffuse deposition of IgA in the mesangium, and electron-dense deposits in the mesangium .
It has became well known that the elevation of serum IgG4 concentration and abundant IgG4-positive plasma cell infiltration in the pancreas are characteristic findings in autoimmune pancreatitis (AIP) , and IgG4-related TIN is also considered to belong to the same disease spectrum. Accordingly, the concept of IgG4-related systemic disease have not been established [1, 5–11], the patients with this diseases share many common features; (1) elevated serum IgG4 level, (2) abundant IgG4-positive plasma cell infiltration in the affected organs, and (3) marked improvement with corticosteroid therapy [5, 7, 9, 10, 12–16]. Our patient exhibited these 3 features. Further, immunohistological studies revealed IgG, IgA, and C3 deposition in the glomeruli resembling IgAN. Although IgA nephropathy associated with MPO-ANCA positive glomerulonephritis has also been reported previously [17, 18], renal biopsy of this case did not show any finding of necrotizing or crescentic glomerulonephritis. This patient had symptoms of HSP systemically. Therefore we made a diagnosis of concomitant HSP nephritis and IgG4-related TIN. Recently, it has been reported that several IgG4-related TIN complicated with glomerular disease [9, 19]. However, this may be the first case of IgG4-related TIN with HSP nephritis.
Allergy research has elucidated the relationship among IgG antibodies, allergens, and the IgG4 subclass in patients undergoing allergen-specific immunotherapy ,, and it has been shown that extended and high-dose exposure to occupational or injected allergens can induce an increase in IgG and IgG4 antibodies and a decrease in IgE antibodies [22–24]. IgG4 is produced in response to repeated exposure to environmental antigens ,. Our patient had been experiencing relapsing HSP for 4 years, and this episode might indicate that he may have been repeatedly exposed to the allergen (Figure 1). Although the nature of the allergen that triggers HSP is unknown, the facts that amounts of IgG were extremely high at the point of purpura development indicate protection with the production of IgG4 might be induced by repetitive allergen exposures, and this hard protection may related with the development of IgG4 related TIN. Nevertheless, HSP developed 3 times, and therefore HSP nephritis might be complicated.
We described a rare case of HSP complicated by concurrent IgG4-related TIN. A biopsy of the collected specimens revealed IgG, IgA, and C3 deposition in the glomeruli and IgG4-producing plasma cell infiltration in the interstitium. We speculate that HSP resulting from repeated allergen exposure might induce the development of IgG4-related TIN and also HSP nephritis.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
This work was supported in part by grants from the Ministry of Education, Science, Technology, Sports and Culture of Japan (HN, KM, and TS) and also supported in part by a grant for the Progressive Renal Diseases Research Projects from the Ministry of Health, Labor and Welfare, Japan (TS).
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