World J Nephrol Urol
World Journal of Nephrology and Urology, ISSN 1927-1239 print, 1927-1247 online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Nephrol Urol and Elmer Press Inc
Journal website http://www.wjnu.org

Case Report

Volume 000, Number 000, January 2016, pages 48-49


Rare Case of Lupus Nephritis With Negative Antinuclear Antibodies, Double-Stranded DNA Antibodies and Positive Anti-Ro/SSA Antibodies

Mohammad Abu-Hishmeha, c, Alamgir Sattara, Z. Zarlashta, Mohamed Ramadana, Aisha J. Abdel-Rahmana, Shante A. Hinsona, b, Nehad Shabareka

aDepartment of Medicine, Lincoln Medical and Mental Health Center, Bronx, NY, USA
bDepartment of Rheumatology, Lincoln Medical and Mental Health Center, Bronx, NY, USA
cCorresponding Author: Mohammad Abu Hishmeh, Department of Medicine, Lincoln Medical and Mental Health Center, 2562 Laconia Ave, Bronx, NY 10469, USA

Manuscript accepted for publication June 24, 2016
Short title: Seronegative Lupus Nephritis
doi: http://dx.doi.org/10.14740/wjnu272e

Abstract▴Top 

Systemic lupus erythematosus (SLE) is an autoimmune multisystem disease that is characterized by various antibodies to nuclear and cytoplasmic antigens and diagnosed by either fulfilling the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria, American College of Rheumatology (ACR) criteria or by Renal Biopsy. Renal involvement is common in SLE and is primarily related to anti-double-stranded DNA antibodies. However, small group of SLE nephritis patients have shown negative anti-dsDNA and ANA. We present a case of 25-year-old female who presented with proteinuria and negative serum antibodies except anti-Ro/SSA. Renal biopsy was performed and was consistent with class IV lupus nephritis (LN). In this report, we highlight the possible role of anti-Ro antibodies in the pathogenesis and the prognosis of LN, although the mechanism is yet to be understood. Anti-Ro/SSA antibodies might play an important role in the pathogenesis and prognosis in LN. However, further studies are required to understand the exact mechanism.

Keywords: Systemic lupus erythematosus; Anti-double-stranded DNA antibodies; Lupus nephritis

Introduction▴Top 

Systemic lupus erythematosus (SLE) is an autoimmune multisystem disease which is diagnosed by either fulfilling the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria, American College of Rheumatology (ACR) or by Renal Biopsy [1]. Renal involvement is a common complication of SLE affecting almost half of the patients [2] and autoantibodies such as anti-dsDNA play a major role in its pathogenesis and activity. In this report, we will discuss a rare case of a young female diagnosed with lupus nephritis (LN), with only anti-Ro/SSA antibodies being positive.

Case Report▴Top 

A 25-year-old female presented to our hospital because of chest pain and frontal headache for 2 weeks, associated with orthopnea, leg swelling and easy fatigability. She had no history of skin rashes, hypersensitivity, fever, oral ulcers, dry mouth or eyes, joint pains, and recent sore throat or skin infections. She had no past medical history and her family history was unremarkable for renal or rheumatological diseases.

On physical examination, her blood pressure was elevated 188/130 mm Hg, and no pedal edema, skin rashes or joint swelling were noted. Her abdominal, respiratory and cardiovascular examination was unremarkable.

Her complete blood count (CBC) showed microcytic anemia with hemoglobin of 9.6 g/dL and mean corpuscular volume of 76 fL, and the leukocyte and platelet counts were normal. The renal function test showed a picture of chronic kidney disease with blood urea nitrogen of 69 mg/dL, serum creatinine of 5.8 mg/dL, low calcium level of 6.9 mg/dL and elevated phosphorus level of 6.9 mg/dL. Her total protein and albumin levels were low at 4.8 and 2.8 g/dL, respectively. The urine studies were significant for 3+ proteinuria, red blood cells and course granular casts. Random urine protein to creatinine ratio was significantly elevated (8.24). Thyroid stimulating hormone and blood glucose levels were normal, and tests for HIV, hepatitis B and hepatitis C were negative. Her serology was positive only for anti-Ro/SSA antibodies by immunoassay 1.8 AI (reference value < 1 AI). ANA, anti-dsDNA, ASO, anti-La, anti-smith and anti-U1RNP antibodies were all negative. Erythrocyte sedimentation rate (ESR) was elevated at 30 mm in the first hour, with normal C-reactive protein of 0.79 mg/L and complement C3 of 115 mg/dL, and her C4 level was elevated at 53 mg/dL.

Renal ultrasound was unremarkable, with right kidney measuring 10.5 cm in length and left kidney measuring 10.2 cm in length. Biopsy of the left kidney was performed under computed tomography guidance, and microscopic evaluation of the specimen showed 11 glomeruli, of which three glomeruli were completely sclerosed, and five glomeruli showed cellular crescent. There was diffuse and prominent interstitial inflammation comprising of lymphocytes and few neutrophils. Ultrastructural evaluation of one glomerulus by electron microscope demonstrated many immune-type electron-dense deposits predominantly at subepithelial and mesangial locations. Unfortunately, no immunofluorescence microscopy evaluation was done because no glomeruli were seen on tissue submitted for immunofluorescence, but the pathology findings were suggestive of proliferative (class IV) LN.

The patient was started on pulse steroid therapy with methyl-prednisone 1 g/day for 3 days then 1 mg/kg of prednisone daily along with mycophenolate and hydroxychloroquine. One month later, hemodialysis was started because of hyperkalemia and fluid overload. After 6 months, the patient is still dependent on hemodialysis and has not shown clinical signs or symptoms of SLE.

Discussion▴Top 

SLE is an autoimmune multisystem disease that is characterized by various antibodies to nuclear and cytoplasmic antigens. Renal involvement is a common complication of SLE affecting almost half of the patients [2]. Although antibodies against DNA play a major role in the pathogenesis and the activity of LN [3-5], there are few cases in the literature of LN with no detectable antibodies [6, 7].

Our patient has a renal biopsy suggestive of LN but did not fulfill the SLICC criteria because there were no antibodies detected except the anti-Ro/SSA which is not part of it. Anti-Ro/SSA antibodies have been associated with Sjogren’s syndrome and neonatal lupus erythematosus (NLE) along with fetal heart conduction abnormalities [8]. The role of anti-Ro/SSA in LN is not established yet, some studies have shown that it has no correlation [9] while others showed that anti-Ro/SSA antibodies alone were associated with a higher prevalence of nephritis [10, 11]. One study has evaluated 130 SLE patients and found that 48% of the patients had anti-Ro/SSA antibodies prior to the diagnosis and were the first antibodies to develop in those patients [12]. In this report, we highlight the possible role of anti-Ro antibodies in the pathogenesis of LN, although the mechanism is yet to be understood.

Conclusion

Anti-Ro/SSA antibodies might play an important role in the pathogenesis and prognosis in LN. However, further studies are required to understand the exact mechanism.


References▴Top 
  1. Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-2686.
    doi pubmed
  2. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, Mejia JC, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore). 2003;82(5):299-308.
    doi pubmed
  3. Yung S, Chan TM. Autoantibodies and resident renal cells in the pathogenesis of lupus nephritis: getting to know the unknown. Clin Dev Immunol. 2012;2012:139365.
    doi pubmed
  4. Egner W. The use of laboratory tests in the diagnosis of SLE. J Clin Pathol. 2000;53(6):424-432.
    doi pubmed
  5. Cameron JS. Lupus nephritis. J Am Soc Nephrol. 1999;10(2):413-424.
    pubmed
  6. Gianviti A, Barsotti P, Barbera V, Faraggiana T, Rizzoni G. Delayed onset of systemic lupus erythematosus in patients with "full-house" nephropathy. Pediatr Nephrol. 1999;13(8):683-687.
    doi pubmed
  7. Simmons SC, Smith ML, Chang-Miller A, Keddis MT. Antinuclear Antibody-Negative Lupus Nephritis with Full House Nephropathy: A Case Report and Review of the Literature. Am J Nephrol. 2015;42(6):451-459.
    doi pubmed
  8. Alexander E, Buyon JP, Provost TT, Guarnieri T. Anti-Ro/SS-A antibodies in the pathophysiology of congenital heart block in neonatal lupus syndrome, an experimental model. In vitro electrophysiologic and immunocytochemical studies. Arthritis Rheum. 1992;35(2):176-189.
    doi pubmed
  9. Alba P, Bento L, Cuadrado MJ, Karim Y, Tungekar MF, Abbs I, Khamashta MA, et al. Anti-dsDNA, anti-Sm antibodies, and the lupus anticoagulant: significant factors associated with lupus nephritis. Ann Rheum Dis. 2003;62(6):556-560.
    doi pubmed
  10. Harley JB, Sestak AL, Willis LG, Fu SM, Hansen JA, Reichlin M. A model for disease heterogeneity in systemic lupus erythematosus. Relationships between histocompatibility antigens, autoantibodies, and lymphopenia or renal disease. Arthritis Rheum. 1989;32(7):826-836.
    pubmed
  11. Wasicek CA, Reichlin M. Clinical and serological differences between systemic lupus erythematosus patients with antibodies to Ro versus patients with antibodies to Ro and La. J Clin Invest. 1982;69(4):835-843.
    doi
  12. Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, Harley JB. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349(16):1526-1533.
    doi pubmed


This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


World Journal of Nephrology and Urology is published by Elmer Press Inc.

 

Browse  Journals  

     

Journal of Clinical Medicine Research

Journal of Endocrinology and Metabolism

Journal of Clinical Gynecology and Obstetrics

World Journal of Oncology

Gastroenterology Research

Journal of Hematology

Journal of Medical Cases

Journal of Current Surgery

Clinical Infection and Immunity

Cardiology Research

World Journal of Nephrology and Urology

Cellular and Molecular Medicine Research

Journal of Neurology Research

International Journal of Clinical Pediatrics

 

 

 

 

 

World Journal of Nephrology and Urology, quarterly, ISSN 1927-1239 (print), 1927-1247 (online), published by Elmer Press Inc.                     
The content of this site is intended for health care professionals.
This is an open-access journal distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution license (Attribution-NonCommercial 4.0 International CC-BY-NC 4.0)


This journal follows the International Committee of Medical Journal Editors (ICMJE) recommendations for manuscripts submitted to biomedical journals,
the Committee on Publication Ethics (COPE) guidelines, and the Principles of Transparency and Best Practice in Scholarly Publishing.

website: www.wjnu.org   editorial contact: editor@wjnu.org
Address: 9225 Leslie Street, Suite 201, Richmond Hill, Ontario, L4B 3H6, Canada
© Elmer Press Inc. All Rights Reserved.


Disclaimer: The views and opinions expressed in the published articles are those of the authors and do not necessarily reflect the views or opinions of the editors and Elmer Press Inc. This website is provided for medical research and informational purposes only and does not constitute any medical advice or professional services. The information provided in this journal should not be used for diagnosis and treatment, those seeking medical advice should always consult with a licensed physician.