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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2016  |  Volume : 27  |  Issue : 6  |  Page : 1270-1273
Decreased sensitivity of anti-dsDNA antibody assay observed in a cohort of Hispanic patients with biopsy-proven lupus nephritis

Department of Medicine, Division of Nephrology, Olive-View UCLA Medical Center, University of California Los Angeles, David Geffen School of Medicine, Department of Medicine, Division of Nephrology, Los Angeles, CA, USA

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Date of Web Publication28-Nov-2016

How to cite this article:
Lopez E, Hanna RM, Wilson J. Decreased sensitivity of anti-dsDNA antibody assay observed in a cohort of Hispanic patients with biopsy-proven lupus nephritis. Saudi J Kidney Dis Transpl 2016;27:1270-3

How to cite this URL:
Lopez E, Hanna RM, Wilson J. Decreased sensitivity of anti-dsDNA antibody assay observed in a cohort of Hispanic patients with biopsy-proven lupus nephritis. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2023 Feb 9];27:1270-3. Available from: https://www.sjkdt.org/text.asp?2016/27/6/1270/194686
To the Editor,

Systemic lupus erythematosus (SLE) is a systemic disease with myriad presentations. Since SLE is an autoimmune process, the susceptibility of the patient to developing complications depends on genetic factors influencing the immune system, recognition of self versus foreign antigens, and suppression of autoimmunity. [1] Recent studies have shown that these processes can differ significantly among different populations. [2],[3] One example is the discovery that certain polymorphisms of interleukin 6 are associated with the development of SLE in Korean patients. [4] Population studies can point out general trends in disease expression within genetically distinct groups, and recent studies of Hispanic patients of American-Indian descent show that these patients tend to have more severe manifestations of SLE. [2]

One of the most ominous complications of SLE is the development of lupus nephritis (LN), as seen in the analysis of the LUMINA XIV Cohort. [5] LN is a very common manifestation of SLE, particularly in those of Hispanic and African ancestry where it occurs in up to 74% of the patients. [1] The literature continues to point out differential risks for the development of LN between different populations as well as different responses to treatment and risks of adverse events.

This is particularly well demonstrated by Isenberg et al from the United Kingdom. It was shown that LN in different ethnicities had different response rates to mycophenolate mofetil and intravenous cyclophosphamide (IVC). Hispanic patients were noted to have the lowest response rate to IVC; 38.8% vs. 60.7% in Caucasian patients. [6] Besides genetic differences, socioeconomic, environmental, cultural, and access to care can predict disease severity as reported by Crosslin et al. [7]

The aforementioned differences make it very important to consider the ethnicity, genetic predisposition, and socio-economic situation of every patient with lupus to help predict prognosis and tailor treatment. It is also important that various diagnostic modalities may be less reliable for different populations. We noted that the anti-Ds DNA antibody test was often negative in several Hispanic patients who later were found to have LN. Thus, we analyzed our database of Hispanic patients with LN to assess the sensitivity of the anti-nuclear antibody (ANA) assay by immunofluorescence assay (IFA) (quest diagnostics) and the sensitivity of the anti-Ds DNA by enzyme immunoassay (EIA) (quest diagnostics) for our population of Hispanic patients with biopsy-proven LN. The biopsy results were also examined and classified according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) Classification scheme for LN. Despite the noted short-falls in the clinical assessment of disease activity, the ISN/RPS scheme has been gaining widespread acceptance due to inter-observer reproducibility and ease of use in SLE patients. [8],[9],[10]

We examined the biopsy results of Hispanic patients suspected to have SLE. A total of 62 biopsies from 54 patients were identified in our initial search; eight patients were biopsied twice. We retrospectively reviewed our electronic records to make sure that these patients had ANA checked by IFA and anti-ds DNA by EIA. Four of these patients had biopsy reports not consistent with LN. Ten patients were eliminated from the analysis because they did not have pre-treatment anti-ds DNA and ANA markers. Thus, 48 biopsies from 40 patients with proven LN and with serological markers were analyzed. We calculated the sensitivity of the ANA by IFA and the anti-ds DNA by EIA in this population and took only one observation from patients who were biopsied twice. We calculated the sensitivity as the number of patients with a positive serological marker divided by the number of patients in the cohort since 100% of our patients had biopsy-proven LN. The pathology results from our 48 biopsies were then classified according to the ISN/RPS 2003 classification system, and the results were plotted in a pie-chart format using Adobe illustrator͹ .

The average age in our cohort of forty patients was 33 years. There were 35 female and five male patients, who were all of Hispanic descent. In our sensitivity calculation, we used our patients with two biopsies as one measurement to avoid a falsely elevated sensitivity. There were 39 patients with positive ANA and 16 patients with positive anti-ds DNA by EIA. The sensitivity of the ANA by IFA in our cohort was 97.5% and the sensitivity of anti-ds DNA by EIA was 40%.

The pathological specimens in patients biopsied twice were temporally separated by at least 12 months and in three instances, the biopsy results differed while in five instances, they fitted in the same ISN/RPS classification. We noted that five patients had crescents on biopsy [Figure 1].
Figure 1: Pathological subtypes of lupus nephritis in the study patients.

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The most common type of histology was diffuse proliferative LN (19%) followed by focal proliferative LN (15%). The most common types of pathological lesions according to the ISN/RPS classification were types IVG-A (28%) and Type IIIA (17%), corresponding to the aforementioned lesions. The percentages were different between the analysis of the pathology and the ISN/RPS classification because there were pathological reports of lesions that may seem slightly different but fit into the same ISN/RPS classification scheme. [10]

As discussed above, it is important to note that different populations of patients show varied expression of autoimmune disease. LN is an ominous development for any lupus patient and portends a poor outcome. Therefore, it is important to detect the disease quickly and accurately to plan treatment appropriately. While medical dictum has generally held that the antids DNA antibody can be useful in the diagnosis of SLE, the data presented have shown that this may have some caveats in Hispanic patients who have LN.

Mok et al have demonstrated the different sensitivities between several markers amongst population groups. [11] The anti-ds DNA, antinucleosome, and anti-C1q antibodies were evaluated, and the reported sensitivity of the antids DNA assay in patients with LN was 75%. [11] This measures up well to the known anti-ds DNA sensitivity of about 70%-90% in the US populations. [12],[13],[14] This may suggest that population differences in sensitivity and specificity of anti-ds DNA exist.

This report, while preliminary , is meant to alert that Hispanic patients with LN may have false-negative anti-ds DNA results. [11] Since the database collected for this study was only for patients with LN, it is not possible to calculate the specificity, which would require a large cohort of patients. Thus, no comment can be made on specificity based on these data, and it is necessary to collect more data in the future to evaluate the specificity of the anti-ds DNA assay in Hispanic patients with LN.

Besides the anti-C1q antibodies and antinucleosome assay noted above, more recently discovered serum markers such as the s-ICAM1 and s-VCAM1 are now being used to diagnose and track the activity of LN. [15] These markers have been found to be markedly elevated in patients with LN and high levels of these markers correlated with decreased complement levels. [15] Furthermore, there was a positive correlation between higher adhesion molecule level and the grade of LN. This disease marker is elevated in the disease state, higher levels correlate with other known markers of disease, and its overall concentration correlates with and predicts disease activity.

The clinical implications of our finding are mainly that if a diagnosis of LN is suspected in a Hispanic patient, a negative anti-ds DNA result does not rule it out and that a biopsy is needed to evaluate the renal pathology.

Conflict of interest: None declared.

   References Top

Ramos PS, Brown EE, Kimberly RP, Langefeld CD. Genetic factors predisposing to systemic lupus erythematosus and lupus nephritis. Semin Nephrol 2010;30:164-76.  Back to cited text no. 1
Calvo-Alén J, Reveille JD, Rodríguez-Valverde V, et al. Clinical, immunogenetic and outcome features of Hispanic systemic lupus erythematosus patients of different ethnic ancestry. Lupus 2003;12:377-85.  Back to cited text no. 2
Burgos PI, McGwin G Jr., Pons-Estel GJ, Reveille JD, Alarcón GS, Vilá LM. US patients of Hispanic and African ancestry develop lupus nephritis early in the disease course: Data from LUMINA, a multiethnic US cohort (LUMINA LXXIV). Ann Rheum Dis 2011;70:393-4.  Back to cited text no. 3
Jeon JY, Kim HA, Kim SH, Park HS, Suh CH. Interleukin 6 gene polymorphisms are associated with systemic lupus erythematosus in Koreans. J Rheumatol 2010;37:2251-8.  Back to cited text no. 4
Danila MI, Pons-Estel GJ, Zhang J, Vilá LM, Reveille JD, Alarcón GS. Renal damage is the most important predictor of mortality within the damage index: Data from LUMINA LXIV, a multiethnic US cohort. Rheumatology (Oxford) 2009;48:542-5.  Back to cited text no. 5
Isenberg D, Appel GB, Contreras G, et al. Influence of race/ethnicity on response to lupus nephritis treatment: The ALMS study. Rheumatology (Oxford) 2010;49:128-40.  Back to cited text no. 6
Crosslin KL, Wiginton KL. The impact of race and ethnicity on disease severity in systemic lupus erythematosus. Ethn Dis 2009;19:301-7.  Back to cited text no. 7
Markowitz GS, D'Agati VD. Classification of lupus nephritis. Curr Opin Nephrol Hypertens 2009;18:220-5.  Back to cited text no. 8
Furness PN, Taub N. Interobserver reproducibility and application of the ISN/RPS classification of lupus nephritis-a UK-wide study. Am J Surg Pathol 2006;30:1030-5.  Back to cited text no. 9
Sada KE, Makino H. Usefulness of ISN/RPS classification of lupus nephritis. J Korean Med Sci 2009;24 Suppl:S7-10.  Back to cited text no. 10
Mok CC, Ho LY, Leung HW, Wong LG. Performance of anti-C1q, antinucleosome, and anti-dsDNA antibodies for detecting concurrent disease activity of systemic lupus erythematosus. Transl Res 2010;156:320-5.  Back to cited text no. 11
El-Chennawi FA, Mosaad YM, Habib HM, ElDegheidi T. Comparative study of antinuclear antibody detection by indirect immunofluorescence and enzyme immunoassay in lupus patients. Immunol Invest 2009;38:839-50.  Back to cited text no. 12
Antico A, Platzgummer S, Bassetti D, Bizzaro N, Tozzoli R, Villalta D; Study Group on Autoimmune Diseases of the Italian Society of Laboratory Medicine (SIMeL). Diagnosing systemic lupus erythematosus: New-generation immunoassays for measurement of anti-dsDNA antibodies are an effective alternative to the Farr technique and the Crithidia luciliae immunofluorescence test. Lupus 2010;19:906-12.  Back to cited text no. 13
Aganovic-Musinovic I, Prljaca-Zecevic L, Subasic D. The incidence of ANA and ETIdsDNA detected by enzyme immunoassays and indirect immunofluorescence assay (IFA). Med Arh 2010;64:68-70.  Back to cited text no. 14
Ilic T, Mitic I, Durdevic-Mirkovic T, Vuckovic B, Milic B, Popovic M. Correlation between sera levels of sICAM-1 and sVCAM-1 and severity of kidney lesions in patients with lupus nephritis. Med Pregl 2007;60 Suppl 2:128-32.  Back to cited text no. 15

Correspondence Address:
Ramy Magdy Hanna
Department of Medicine, Division of Nephrology, Olive-View UCLA Medical Center, University of California Los Angeles, David Geffen School of Medicine, Department of Medicine, Division of Nephrology, Los Angeles, CA
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.194686

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