The possible involvement of intestine-derived IgA 1 : a case of IgA nephropathy associated with Crohn’s disease
Terasaka et al. BMC Nephrology
The possible involvement of intestine- derived IgA : a case of IgA nephropathy 1 associated with Crohn's disease
Tomohiro Terasaka 1 2
Haruhito A. Uchida 0 1 2
Ryoko Umebayashi 1 2
Keiko Tsukamoto 1 2
Keiko Tanaka 1 2
Masashi Kitagawa 1 2
Hitoshi Sugiyama 1 2 3
Hiroaki Tanioka 2 4
Jun Wada 1 2
0 Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 , Japan
1 Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 , Japan
2 Abbreviations: ASA , 5-aminosalicylic acid; AZA, Azathioprine; HLA, Human leukocyte antigen; IBD, Inflammatory bowel disease; IgA, Immunoglobulin A; IgG, Immunoglobulin G; IgM, Immunoglobulin M; TIN, Tubulointerstitial nephritis
3 Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 , Japan
4 Department of Medicine Oncology, Okayama Rosai Hospital , 1-10-25 Chikkomidori-machi, Minami-ku, Okayama 702-8055 , Japan
Background: A link between IgA nephropathy and Crohn's disease has recently been reported. Other researchers hypothesize that intestine-derived IgA complexes deposit in glomerular mesangial cells, eliciting IgA nephropathy. Intestinal mucosal plasma cells mainly secrete IgA2. Nevertheless, IgA1 deposition is strongly implicated as being the primary cause of IgA nephropathy. Case presentation: A 46-year-old Japanese man developed IgA nephropathy 29 years ago, following tonsillectomy. As a result, a normal urinalysis was obtained. The patient previously suffered Crohn's disease followed by urinary occult blood and proteinuria six years ago. Exacerbation of IgA nephropathy was highly suspected. Therefore a renal biopsy was performed. A diagnosis of exacerbation of IgA nephropathy with mesangial cell proliferation and fibrotic cellular crescent was based upon the pathological findings. The patient exhibited a positive clinical course and eventually achieved a remission with immunosuppressive therapy including prednisolone treatment. Immunostaining for the detection of IgA subtypes was performed on both of his kidney and excised ileum. The results revealed IgA1 and IgA2 deposition by submucosal cells in intestine. Furthermore, IgA1 deposition of mesangial areas in the patient's kidney, indicated an association of IgA1 with the exacerbation of IgA nephropathy. Conclusion: This case represents the possibility that the intestine-derived IgA1 can be the origin of galactose-deficient IgA which is known to cause IgA nephropathy exacerbation.
Crohn's disease; IgA nephropathy; IgA1; IgA2; Inflammatory bowel disease
Background
IgA1 is one of the subtypes of IgA produced in bone
marrow, tonsils and respiratory tracts. Also, it can be found
predominantly in the glomeruli of patients with IgA
nephropathy. This observation supports the idea of using
tonsillectomy as an effective therapeutic intervention for
IgA nephropathy. Alternatively, intestinal mucosal plasma
cells mainly secrete IgA2 (approximately 60 % in mucosal
cells), another subtype of IgA, rather than IgA1 [
1
].
Recent reports have indicated a strong link between
IgA nephropathy and Crohn’s disease. Several
hypotheses exist, indicating this, however the underlying
mechanism is still unknown. One can speculate that
intestine-derived IgA is possibly deposited in
glomerular mesangial cells, eliciting IgA nephropathy [
2–4
].
Here, we present a case report of a patient suffering
from exacerbated IgA nephropathy associated with
Crohn’s disease, who had tonsillectomy 29 years ago.
We performed immunohistochemical analysis in renal
biopsy and excised ileum specimen to determine
whether it was IgA1 or IgA2 that was specifically
associated with the exacerbation of IgA nephropathy. The
results indicated that IgA1, not IgA2, is the causative
source of IgA nephropathy exacerbation. This indicates
a link between inflammatory intestine-derived IgA1 and
IgA nephropathy.
Case presentation
A 46-year-old Japanese man suffered from IgA
nephropathy, prior to be given tonsillectomy 29 years ago.
Urinalysis revealed neither hematuria nor proteinuria after
surgical removal of his tonsils. The patient experienced a
sudden onset of Crohn’s disease 6 years ago. As a result,
he was administered several medications to alleviate the
symptoms of Crohn’s disease; initially, 5-aminosalicylic
acid (ASA). Due to the unstable state of Crohn’s disease,
an ileum resection was performed. Additionally,
prednisolone, azathioprine (AZA) and infliximab were eventually
incorporated in his treatment. Despite therapeutic drug
intervention, his abdominal symptoms including diarrhea
persisted. C (...truncated)