Urine 2-microglobulin was 32550?g/day time (normal, below 250), and N-acetyl–D-glucosaminidase was 17

Urine 2-microglobulin was 32550?g/day time (normal, below 250), and N-acetyl–D-glucosaminidase was 17.9 U/L (normal, 0.3 to 11.5). Summary Neither drug reactions nor collagen disease were likely causes of tubular interstitial disorder with this patient. Although BK Rabbit Polyclonal to RAB41 disease was ruled out, IgG in the -globulin preparation might have reacted having a pathogen present in the patient to form low-molecular-weight immune complexes that were deposited in the tubular basement membrane. strong class=”kwd-title” Keywords: Bruton agammaglobulin tyrosine kinase (BKT) gene, Immune complexes, Steroid therapy, Tubular deposition, Tubular atrophy Background In X-linked agammaglobulinemia (XLA), mutation involving the Bruton agammaglobulin tyrosine kinase (BTK) gene induces a B-cell maturation disorder that causes congenital immunodeficiency in which repeated bacterial infections reflect antibody production failure [1,2]. Prognosis for survival is relatively beneficial owing to immunoglobulin alternative therapy (intravenous immunoglobulin therapy, or IVIG) [3]. We experienced a patient with BTK gene mutation (p.Gln412X)-induced XLA who formulated renal dysfunction associated with increased urinary 2-microglobulin during IVIG therapy. Renal histology indicated a tubular interstitial disorder. Glomerular immune complex deposition such as in membranous nephropathy [4] and membranoproliferative glomerulonephritis [5] occasionally has been reported in association with IVIG therapy for XLA. To our knowledge, however, tubulointerstitial nephritis Y15 (TIN) showing immune complex deposition in the tubular basement membrane has not previously been reported in XLA individuals receiving IVIG therapy. Case demonstration A 20-year-old man who was diagnosed with XLA 3?weeks after birth was treated periodically with IVIG. Mild renal dysfunction developed at 19?years. Serum creatinine (Cr) and blood urea nitrogen (BUN) were 1.5 and 30?mg/dL respectively, and urinary 2-microglobulin was elevated. The patient was admitted to our division for further evaluation and treatment. Urinalysis on admission showed specific gravity of 1 1.017, 1+ qualitative protein, and 0.14?g/day time quantitative protein. Microscopy showed 1 to 4 reddish blood cells per high-power field (HPF). White colored blood cells were 1 to 4 per HPF. Urine 2-microglobulin was 32550?g/day time (normal, below 250), and Y15 N-acetyl–D-glucosaminidase was 17.9 U/L (normal, 0.3 to 11.5). Creatinine clearance was 39.2?mL/min/1.73?m2 (normal, 65 to 142). The findings suggested tubular interstitial disorder causing renal dysfunction. No uveitis was recognized. On hematologic exam, the red blood cell count was 548 104 /L; white blood cell count, 8400 /L; platelet count, 15.5 104/L; and erythrocyte sedimentation rate, 4?mm/hour. In serum, Na was 142?mEq/L; K, 3.9?mEq/L; C-reactive protein, 2.8?mg/dL; BUN, 30?mg/dL; Cr, 1.29?mg/dL; and cystatin C, 1.96?mg/L (normal, 0.56 to 0.87). In sum, inflammatory markers were mildly elevated and moderate renal dysfunction was present. The IgG concentration was 685?mg/dL (normal, 870 to 1700?mg/dL); and IgM, below 20?mg/dL (normal, 33 to 190?mg/dL). Match components were normal. Serum IgG4 Y15 concentration was below 1% of total serum IgG concentration. All autoantibodies were absent (antinuclear, anti-DNA, rheumatoid arthritis hemagglutination antibodies, anti-cyclic citrullinated peptide, anti-SS-A/Ro, anti-SS-B/La, and myeloperoxidase-ANCA). On investigation for pathogens, cytomegalovirus pp65 antigen, anti-VCA IgM antibody, and -interferon specific for tuberculosis were not detected. Adenovirus, herpes simplex virus, and BK disease were not recognized by real-time polymerase chain reaction. Lymphocyte activation checks (DLST) with D-mannitol, glycine, and polyethylene glycol (all components of the individuals -globulin preparation) were bad. No physical, laboratory, or radiologic findings suggesting Castleman disease or malignant lymphoma were demonstrated.Examination of renal biopsy specimen showed marked mononuclear cell infiltration in the interstitium (Number?1a), and loss of tubular epithelial cells, cloudy degeneration, and irregularity of the basement membrane in some renal tubules. Some glomeruli showed cellular crescent formation (Number?1b) and fibrosclerotic lesions. Fluorescent antibody staining recognized granular depositions of IgG (Number?1c) and match component C3 in the tubular basement membrane. By electron microscopy (Number?1d), electron-dense deposits were observed in the tubular basement membrane. Immune cells infiltrating in the tubulointerstitium were mainly Y15 CD3 antigen-positive lymphocytes (T-cells; Number?1e), but not IgG4-bearing cells (Number?1f). Open in a separate window Number 1 Renal histologic findings in the patient. Marked tubulointerstitial mononuclear cell infiltration was observed (a; Masson trichrome stain, 100). Crescent formation was noted in some glomeruli (b; periodic acid-Schiff stain, 200). Fluorescent antibody staining shown granular deposition of IgG in the tubular basement membrane (c; 200). Electron-dense deposits were present in the tubular basement membrane (d; unique magnification, 6000). Immune cells infiltrating in tubulointerstitial cells were mainly CD3-positive T-cells (e), as opposed to IgG4-bearing cells (f; 200). Steroid therapy was.