Sirs,

I read with interest the article in this journal entitled “C1q nephropathy in association with Gitelman syndrome: a case report” by Hanevold et al. [1]. The presence of C1q nephropathy and Gitelman syndrome in the reported patient may be coincidental as the authors suggested. It is possible, however, that some form of immunologic derangement caused by the SLC12A3 gene mutation may have facilitated the development of immune complex-mediated glomerulonephritis in this patient.

We previously reported a patient who developed a second episode of acute poststreptococcal glomerulonephritis (APSGN) [2]. Recurrence of APSGN is a rare phenomenon, due to the acquisition of protective immunity against a nephritogenic streptococcal antigen after an initial episode of APSGN [3]. Nephritis-associated plasmin receptor (NAPlr), a nephritogenic antigen isolated from the group A streptococcus, is observed in APSGN kidney biopsy specimens in the early stage of the disease [4]. Also, circulating anti-NAPlr antibodies are present in most patients with APSGN, and antibody titers remain elevated for a prolonged period following the onset of APSGN [4]. Our patient did not have anti-NAPlr antibodies despite the presence of NAPlr in the kidney biopsy specimen, thereby suggesting the absence of a natural immune response to the NAPlr probably due to some genetic abnormalities [1]. Interestingly, the mother of our patient was diagnosed with Gitelman syndrome and exhibited a heterozygous frame-shift mutation in the SLC12A3 gene [5]. Because Gitelman syndrome is an autosomal recessive disease [6], the mother of our patient has compound heterozygous mutations of SLC12A3 such that our patient has a heterozygous mutant allele of SLC12A3.

Although the precise role of the SLC12A3 gene mutation in the development of the second attack of APSGN in our patient is unclear, SLC12A3 gene mutations may result in immunologic abnormalities including the absence of a natural immune response to NAPlr. Further studies are necessary to determine whether SLC12A3 mutations exhibit immunologic abnormalities that promote the development of glomerulonephritis, including C1q nephropathy.