Interstitial nephritis with infiltration of IgG-kappa positive plasma cells in a patient with Sjögren's syndrome

J. Pijpe, A. Vissink, J. E. Van der Wal1 and C. G. M. Kallenberg2

Departments of Oral Maxillofacial Surgery, 1Pathology and 2Clinical Immunology, University Hospital Groningen, Groningen, The Netherlands

Correspondence to: J. Pijpe, Department of Oral and Maxillofacial Surgery, PO box 30.001, 9700 RB Groningen, The Netherlands. E-mail: j.pijpe{at}kchir.azg.nl

SIR, Sjögren's syndrome (SS) is an autoimmune disease involving the exocrine glands. It is characterized by lymphocytic infiltration of the exocrine glands and polyclonal B-cell activation. The main symptoms are dry eyes, dry mouth and fatigue, but a variety of other manifestations can also occur. Interstitial nephritis is the principal renal lesion in SS, and occurs in approximately 10% of the patients [1, 2]. Immunohistology shows infiltration of mainly CD4+ T lymphocytes, comparable with those observed in the salivary glands [3]. We describe here a patient (informed consent for publication was obtained) with primary SS, who presented with interstitial nephritis with an IgG-kappa positive B-cell proliferation in the kidney. This type of monoclonal B-cell proliferation localized in the kidney in a patient with SS has not been reported before.

A 60-yr-old woman was referred to the departments of clinical immunology and oral and maxillofacial surgery because of suspicion of primary SS. She was diagnosed elsewhere with IgG-kappa paraproteinaemia 4 yr previously. On admission, she complained of progressive fatigue, eye dryness and mouth dryness. Physical examination showed no enlargement of the parotid glands, no palpable lymph nodes in the head and neck region, and no hepato- or splenomegaly.

Some laboratory data are given in Table 1. In addition, creatinine clearance was decreased (60 ml/min), with a slight proteinuria of 0.3 g/24 h, and in the urine sediment persistent leucocyturia, but no casts. Immunoelectrophoresis and immunofixation revealed an IgG-kappa paraprotein. Bence-Jones protein was present in the urine. Unstimulated and stimulated (2% citric acid) whole saliva flow rates were reduced. Parotid sialography showed punctate sialectasia. She refused a salivary gland biopsy. The Schirmer test was less than 5 mm/5 min (normal value >10 mm/5 min).


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TABLE 1. Laboratory data

 
A bone marrow biopsy showed 5–10% plasma cells, all positive for kappa light chains. There were no solid lymphoid or plasma cell infiltrations. No lytic bone lesions were seen on a plain radiographic image of the whole skeleton. The IgG-kappa paraproteinaemia was therefore diagnosed as monoclonal gammopathy of undetermined significance (MGUS).

A renal biopsy showed normal glomeruli without immune deposits, and a diffuse inflammatory infiltrate in the tubulo-interstitium, mainly consisting of plasma cells and some small CD3+ lymphocytes (Figure 1). There were areas with tubular atrophy and some interstitial fibrosis. Immunohistochemistry of the plasma cells showed domination of kappa-positive plasma cells in the interstitium, with few lambda-positive cells (Figures 2 and 3).



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FIG. 1. Renal biopsy showing diffuse inflammatory infiltrate (arrow) (periodic acid–Schiff staining, magnification x40).

 


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FIG. 2. Immunohistochemical staining for kappa light chain, showing a predominance of kappa-positive plasma cells (arrows) compared with lambda-positive plasma cells (Fig. 3) (magnification x40).

 


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FIG. 3. Immunohistochemical staining for lambda light chain showing just a few lambda-positive plasma cells (arrow) (magnification x40).

 
In conclusion, this patient presented with primary SS (according to the revised European–American diagnostic criteria [4]), with interstitial nephritis with IgG-kappa light chain plasma cell infiltration. The IgG-kappa paraproteinaemia was diagnosed as MGUS. Treatment was started with prednisolone at 30 mg daily. The erythrocyte sedimentation rate (ESR) decreased to 25 mm/h and creatinine to 119 µmol/l; clearance improved. Levels of immunoglobulins and rheumatoid factor decreased, the paraprotein remained stable. At present, 2 yr later, the patient is on 5 mg of prednisolone. Renal function is stable, but there is slight persisting leucocyturia. There are no signs of malignant lymphoma or plasmacytoma.

SS represents a spectrum from benign to malignant lymphoproliferation. It is generally accepted that the affected exocrine glands are the main area of monoclonal B-lymphocyte activity [5]. Polyclonal hypergammaglobulinaemia is common; monoclonal gammopathy has been described sporadically [68]. Our patient presented with IgG-kappa paraproteinaemia, leucocyturia and mild renal insufficiency. A lymphoplasma cellular infiltrate was present in the renal biopsy, with a clonal IgG-kappa light chain B-cell proliferation, instead of the normal majority of activated CD4+ T lymphocytes. Multiple myeloma was suspected, but was considered unlikely, because less then 10% marrow plasmacytosis was found, there were no lytic bone lesions, and because of the benign clinical course for 4 yr. The paraproteinaemia was interpreted as MGUS, probably owing to the clonal population localized in the kidney and the bone marrow.

Interstitial nephritis is a common finding in patients with SS, with infiltration of mainly T lymphocytes [13]. Clinical manifestations are a, generally mild, elevation in plasma creatinine concentration, leucocyturia and slight proteinuria. Therapy usually consists of steroids. When a clonal B-cell population is present, multiple myeloma or malignant lymphoma should be considered. Although patients with SS have an increased risk of developing non-Hodgkin's lymphoma, biopsy specimens do not always meet histological criteria for malignancy. These infiltrates have been called ‘pseudolymphomas’, and have been described in the kidney, lung, ureter and liver [9, 10]. Pseudolymphoma refers to extensive lymphocytic infiltration with dysruption of normal architecture, but without cytological atypia. The majority of lymphocytes in pseudolymphoma associated with SS are T cells. Only a few incidental cases of renal pseudolymphoma have been described [9], which dramatically responded to steroid therapy. The present type of monoclonal infiltration leading to interstitial nephritis in a patient with SS, with a similar therapeutic response, has not been described before.

The authors have declared no conflicts of interest.


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Accepted 29 April 2003





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