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Autoantibodies against intercalated cells in Sjögren's syndrome
letter to the editor
http://www.kidney-international.org & 2009 International Society of Nephrology
Autoantibodies against intercalated cells in Sjo¨gren’s syndrome Kidney International (2009) 76, 229; doi:10.1038/ki.2009.112
To the Editor: Recently, Bae et al.1 reported on a 43-year-old woman presenting with distal renal tubular acidosis (dRTA) associated with Sjo¨gren’s syndrome. Confirming earlier
reports,2–4 they showed decreased immunostaining for H þ ATPase in the cortical collecting duct of the patient. The cause of the reduced expression of H þ -ATPase in intercalated cells (ICs) of dRTA kidneys in Sjo¨gren’s syndrome is unknown. A 29-year-old woman with sicca syndrome presented with hypokalemia (2.4 mEq/l), hyperchloremic metabolic acidosis (plasma HCO 3 13 mEq/l), inappropriate urine (pH 7.0), positive urinary anion gap (þ 21 mEq/l), and normal renal function. She had polyclonal hypergammaglobulinemia, positive antinuclear antibodies and anti-Ro/SS-A, and inflammatory infiltrates in the parotid gland biopsy. On bicarbonate loading, FEHCO3 was o5%, with a low (urinary–blood) DpCO2 (13 mm Hg), suggesting defective H þ secretion by A-type IC. The kidney biopsy revealed mild inflammatory cell infiltrates, without interstitial fibrosis. Compared with control kidneys, a strong attenuation of H þ -ATPase immunoreactivity was observed both in the proximal tubule and in the collecting duct profiles (Figure 1a and b). In particular, no ICs positive for H þ -ATPase were detectable, although ICs could be identified by electron microscopy (Figure 1c–f). Importantly, the immunoglobulin G purified from the dRTA patient detected ICs in collecting duct profiles of human control kidneys (Figure 1g–k). These data reveal that patients with Sjo¨gren’s syndrome may present autoantibodies directed against the A-type IC of the human kidney. Identifying these antigens could improve our understanding of the role of IC cells and the pathophysiology of dRTA. ACKNOWLEDGMENTS
The authors acknowledge the EUNEFRON (FP7, GA no. 201590) program of the European Community. 1. 2.
3.
Figure 1 | Intercalated cells in Sjo¨gren’s syndrome. Immunostaining for H þ -ATPase in normal human kidney (a) and the distal renal tubular acidosis (dRTA) patient (b, d), showing a decreased immunoreactivity in both the proximal tubule (pt) and collecting duct (cd) profiles. Staining for AQP2 on serial sections from the dRTA kidney (c, d) shows a lack of intercalated cells (ICs) positive for H þ -ATPase in the collecting ducts. Panels (e) (semi-thin section, toluidine blue) and (f) (ultra-thin section, uranyl acetate and lead citrate) reveal apparently normal ICs in the dRTA kidney. Incubation of control human kidneys with immunoglobulin G (IgG) extracted from the dRTA patient stained ICs in collecting ducts (g, h: asterisks). The A-type ICs stained with the auto-antibodies (h) were positively identified on serial sections with apical H þ -ATPase (i) and basolateral AE1 (j), whereas no signal was obtained with control human IgG (k). Immunostaining was performed as in Moulin et al.5 Original magnification (a–e, g) 20; (h–k) 40; (f) bar ¼ 2 mm.
Kidney International (2009) 76, 229–231
4.
5.
Bae EH, Han CW, Lee JH et al. Hypokalemia associated with nephrocalcinosis. Kidney Int 2009; 75: 443–444. Cohen EP, Bastani B, Cohen MR et al. Absence of H(+)-ATPase in cortical collecting tubules of a patient with Sjogren0 s syndrome and distal renal tubular acidosis. J Am Soc Nephrol 1992; 3: 264–271. DeFranco PE, Haragsim L, Schmitz PG, Bastani B. Absence of vacuolar H(+)-ATPase pump in the collecting duct of a patient with hypokalemic distal renal tubular acidosis and Sjo¨gren’s syndrome. J Am Soc Nephrol 1995; 6: 295–301. Han JS, Kim GH, Kim J et al. Secretory-defect distal renal tubular acidosis is associated with transporter defect in H(+)-ATPase and anion exchanger-1. J Am Soc Nephrol 2002; 13: 1425–1432. Moulin P, Igarashi T, Van Der Smissen P et al. Altered polarity and expression of H+-ATPase without ultrastructural changes in kidneys of Dent’s disease patients. Kidney Int 2003; 63: 1285–1295.
Olivier Devuyst1, Matthieu Lemaire1, Nilufar Mohebbi2 and Carsten A. Wagner2 1 Division of Nephrology, Universite´ Catholique de Louvain Medical School, Brussels, Belgium and 2Institute of Physiology and Zurich Center for Human Integrative Physiology, University of Zurich, Zurich, Switzerland Correspondence: Olivier Devuyst, Division of Nephrology, Universite´ Catholique de Louvain Medical School, 10 Avenue Hippocrate, Brussels B-1200, Belgium. E-mail: [email protected]
229
http://www.kidney-international.org & 2009 International Society of Nephrology
Autoantibodies against intercalated cells in Sjo¨gren’s syndrome Kidney International (2009) 76, 229; doi:10.1038/ki.2009.112
To the Editor: Recently, Bae et al.1 reported on a 43-year-old woman presenting with distal renal tubular acidosis (dRTA) associated with Sjo¨gren’s syndrome. Confirming earlier
reports,2–4 they showed decreased immunostaining for H þ ATPase in the cortical collecting duct of the patient. The cause of the reduced expression of H þ -ATPase in intercalated cells (ICs) of dRTA kidneys in Sjo¨gren’s syndrome is unknown. A 29-year-old woman with sicca syndrome presented with hypokalemia (2.4 mEq/l), hyperchloremic metabolic acidosis (plasma HCO 3 13 mEq/l), inappropriate urine (pH 7.0), positive urinary anion gap (þ 21 mEq/l), and normal renal function. She had polyclonal hypergammaglobulinemia, positive antinuclear antibodies and anti-Ro/SS-A, and inflammatory infiltrates in the parotid gland biopsy. On bicarbonate loading, FEHCO3 was o5%, with a low (urinary–blood) DpCO2 (13 mm Hg), suggesting defective H þ secretion by A-type IC. The kidney biopsy revealed mild inflammatory cell infiltrates, without interstitial fibrosis. Compared with control kidneys, a strong attenuation of H þ -ATPase immunoreactivity was observed both in the proximal tubule and in the collecting duct profiles (Figure 1a and b). In particular, no ICs positive for H þ -ATPase were detectable, although ICs could be identified by electron microscopy (Figure 1c–f). Importantly, the immunoglobulin G purified from the dRTA patient detected ICs in collecting duct profiles of human control kidneys (Figure 1g–k). These data reveal that patients with Sjo¨gren’s syndrome may present autoantibodies directed against the A-type IC of the human kidney. Identifying these antigens could improve our understanding of the role of IC cells and the pathophysiology of dRTA. ACKNOWLEDGMENTS
The authors acknowledge the EUNEFRON (FP7, GA no. 201590) program of the European Community. 1. 2.
3.
Figure 1 | Intercalated cells in Sjo¨gren’s syndrome. Immunostaining for H þ -ATPase in normal human kidney (a) and the distal renal tubular acidosis (dRTA) patient (b, d), showing a decreased immunoreactivity in both the proximal tubule (pt) and collecting duct (cd) profiles. Staining for AQP2 on serial sections from the dRTA kidney (c, d) shows a lack of intercalated cells (ICs) positive for H þ -ATPase in the collecting ducts. Panels (e) (semi-thin section, toluidine blue) and (f) (ultra-thin section, uranyl acetate and lead citrate) reveal apparently normal ICs in the dRTA kidney. Incubation of control human kidneys with immunoglobulin G (IgG) extracted from the dRTA patient stained ICs in collecting ducts (g, h: asterisks). The A-type ICs stained with the auto-antibodies (h) were positively identified on serial sections with apical H þ -ATPase (i) and basolateral AE1 (j), whereas no signal was obtained with control human IgG (k). Immunostaining was performed as in Moulin et al.5 Original magnification (a–e, g) 20; (h–k) 40; (f) bar ¼ 2 mm.
Kidney International (2009) 76, 229–231
4.
5.
Bae EH, Han CW, Lee JH et al. Hypokalemia associated with nephrocalcinosis. Kidney Int 2009; 75: 443–444. Cohen EP, Bastani B, Cohen MR et al. Absence of H(+)-ATPase in cortical collecting tubules of a patient with Sjogren0 s syndrome and distal renal tubular acidosis. J Am Soc Nephrol 1992; 3: 264–271. DeFranco PE, Haragsim L, Schmitz PG, Bastani B. Absence of vacuolar H(+)-ATPase pump in the collecting duct of a patient with hypokalemic distal renal tubular acidosis and Sjo¨gren’s syndrome. J Am Soc Nephrol 1995; 6: 295–301. Han JS, Kim GH, Kim J et al. Secretory-defect distal renal tubular acidosis is associated with transporter defect in H(+)-ATPase and anion exchanger-1. J Am Soc Nephrol 2002; 13: 1425–1432. Moulin P, Igarashi T, Van Der Smissen P et al. Altered polarity and expression of H+-ATPase without ultrastructural changes in kidneys of Dent’s disease patients. Kidney Int 2003; 63: 1285–1295.
Olivier Devuyst1, Matthieu Lemaire1, Nilufar Mohebbi2 and Carsten A. Wagner2 1 Division of Nephrology, Universite´ Catholique de Louvain Medical School, Brussels, Belgium and 2Institute of Physiology and Zurich Center for Human Integrative Physiology, University of Zurich, Zurich, Switzerland Correspondence: Olivier Devuyst, Division of Nephrology, Universite´ Catholique de Louvain Medical School, 10 Avenue Hippocrate, Brussels B-1200, Belgium. E-mail: [email protected]
229