IgG4-related disease should be considered in cases of hypocomplementemic immune-complex tubulointerstitial nephritis

Dear Sir, We read with great interest the paper of Gupta et al. concerning a case of hypocomplementaemic tubulointerstitial nephritis (TIN) [1]. Hypocomplementaemic immune complex TIN in the absence of autoimmune disorders is a rare condition, and only a limited number of cases have been reported, of which most have been labelled idiopathic [2]. However, in recent years, several case reports and case studies of immunoglobulin G4 (IgG4)-related disease as the cause of hypocomplementaemic immune complex TIN have been published, and we are convinced that this should be considered in the case presented here [3]. IgG4-related disease is a systemic disease characterized by multi-organ infiltration by IgG4 plasmocytes, which can affect pancreas, lacrimal glands, lymph nodes, lung and renal tissue, and has been associated with Mikulicz's disease, Sjögren's syndrome, hypothyroidism, interstitial pneumonia, retroperitoneal fibrosis, sclerosing cholangitis and primary biliary cirrhosis. Elevated levels of serum IgG4 and infiltration of IgG4-positive plasma cells are the hallmarks of this disease entity [4]. TIN is the most common pattern of renal involvement associated with IgG4-related disease; however, extraparenchymal involvement with hydroureteronephrosis due to retroperitoneal fibrosis and glomerular disease (membranous and membranoproliferative glomerulonephritis) have also been reported [3]. Typically, this disease tends to respond favourably to steroid therapy. Besides hypocomplementaemia and elevated serum IgG4, antinuclear (ANF) positivity is a near universal finding in patients with IgG4-related disease. Most patients have no detectable anti-double-stranded DNA antibodies, although the presence of other autoantibodies has been described in these patients [4]. To our knowledge, a positive perinuclear-antineutrophil cytoplasmic antibody (pANCA) has not been reported. The precise pathogenesis of IgG4-related disease is unknown at present [4]. IgG4 is the rarest IgG subclass, and elevated titres of IgG4 are found in pemphigus foliaceus, pemphigus vulgaris, asthma bronchiale, atopic dermatitis and allergy. IgG4 is unable to fix and activate complement, and as such, IgG4 is believed to represent an anti-inflammatory antibody. The identity of the target autoantigen in IgG4-related disease is unclear, although Aoki et al. found IgG4 autoantibody reactivity directed towards the pancreatic duct epithelium, bile duct epithelium and salivary gland duct epithelium [5]. And thus, the demonstration of deposits of immune complexes along the tubular basement membrane suggests that the causative renal antigen might be localized at this site. In conclusion, we think that IgG4-related disease should be considered in the cases of hypocomplementaemic immune complex TIN.