Brief Report: A Novel Application of Buccal Micronucleus Cytome Assay in Systemic Lupus Erythematosus: A Case–Control Study

Abstract

Objective. Systemic lupus erythematous (SLE) is a systemic autoimmune disease, and both genetic and environmental factors are implicated in its pathogenesis. The aim of this study was to assess cellular and nuclear morphology of SLE using a buccal micronucleus cytome assay.Methods. This study included 58 SLE patients and 58 healthy age-and sex-matched controls. Patients' baseline characteristics were recorded, and a buccal micronucleus cytome assay was used to measure cellular and nuclear abnormalities in both groups.Results. Significantly higher frequencies of micronuclei, nuclear buds, binucleated cells, basal cells, condensed chromatin cells, karyorrhectic cells, pyknotic cells, and karyolytic cells were seen in SLE patients as compared to controls. A buccal micronucleus cytome assay score of >4 had the highest accuracy (93.1%), almost perfect positive predictive value (98.1% at 50% pretest probability and 99.8% at 90% pretest probability), 87.9% sensitivity, and 98.3% specificity for the diagnosis of SLE.Conclusion. Biomarkers of DNA damage, proliferative potential, and cell death were significantly increased in SLE patients. The buccal micronucleus cytome assay was a valid and easy way for clinicians to assess individuals at high risk of developing SLE.Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with a variety of proposed pathogeneses. Apoptosis is one of several important mechanisms involved in the pathogenesis of SLE. A previous study has demonstrated that lymphocyte apoptosis is increased and removal of apoptotic cells is impaired in SLE. Furthermore, apoptosis was found to be higher in active SLE as compared to inactive SLE (1).Several lines of evidence have demonstrated the close relationship between apoptosis and autoantibodies. Delayed clearance of apoptotic residue, such as histone H3, may result in the activation of antigenpresenting cells and the formation of autoantibodies; further, the antigenicity of autoantibodies is mostly against apoptotic cells (2). Studies have linked lymphocyte and leukocyte apoptosis with SLE and titers of autoantibodies (3).The buccal micronucleus cytome assay is a noninvasive method used to study DNA damage, chromosomal instability, cell death, and the regenerative potential of human buccal mucosal tissue (4). To our knowledge, no studies have as yet assessed buccal cell micronuclei in patients with connective tissue diseases or inflammatory arthritis. This study was designed to assess cellular and nuclear morphology in SLE using a buccal micronucleus cytome assay. PATIENTS AND METHODSStudy design. This case-control study was conducted at the Baghdad Teaching Hospital Rheumatology Unit from September 2012 to May 2013. We screened SLE patients who were eligible for inclusion in the study and then compared patients to matched healthy controls; buccal micronucleus cytome biomarkers were measured in both groups. Informed consent was obtained from all participants, and this study was approved by the ethics committee of Baghdad University, College...

Clinical application of micronucleus test in exfoliated buccal cells: A systematic review and metanalysis

“…The MN assay, as marker of chromosome breakage and chromosome loss, has been envisaged as a promising candidate in this perspective. Consistently higher frequencies of MN in the lesion area compared with normal tissue (56,58,59) and in association with the histological grade of oral carcinomas (59) were observed in patients with cancer and preneoplastic diseases.…”

“…A total of 56 full-text articles were assessed for eligibility. Forty-two of them met the criteria to be included in the systematic review, while the remaining studies were excluded due to lack of control group (18, 51-53) of data about MN values(54)(55)(56) or because they report only results on treated patients(57) or not related to specific diseases(58). Five low-size studies on patients with different genetic diseases were not included in our review(13)(14)(15)(16)59) …”

Genotoxic Effect in Autoimmune Diseases Evaluated by the Micronucleus Test Assay: Our Experience and Literature Review

“…They analyzed the effect of CYC and the influence of CYP2D6 polymorphisms on MN formation in patients with SLE; they found that the genotoxicity is increased in patients with SLE after CYC boluses without an association with the CYP2D6 allele expression, which contributes to the idea that irrespective from treatments patients with AD exhibit higher MN formation when compared to healthy subjects. The most recent study in this field was published in 2014 by Al-Rawi et al [ 30 ]; after assessing nuclear morphology in 58 SLE patients and 58 healthy age- and sex-matched controls by the use of buccal micronucleus cytome assay, they proposed a score with a cutoff value of ≥4 that exhibited a high accuracy (93.1%), higher positive predictive value (98.1% at 50% pretest probability and 99.8% at 90% pretest probability), sensitivity of 87.9%, and specificity of 98.3% for the diagnosis of SLE. After these findings, they concluded that the buccal micronucleus cytome assay was a valid and easy way for clinicians to assess individuals at high risk for developing SLE, since a negative result in the total micronuclei count excluded a possible diagnosis of SLE with 98.9% confidence in a clinical setting in which the differential diagnosis of SLE was of low probability (10% pretest probability).…”

Correlation of buccal micronucleus with disease activity score using buccal micronucleus cytome analysis (BMCA) in systemic lupus erythematosus

“…The results of our current study showed no significant difference in the mean values of MN frequency in patients with SLE (RG) versus healthy individuals (CG) ( P = 0.057). [ 22 ] The variation in our results could be attributed to the fact that patients were undergoing medical treatment before the start of the study, and therefore their SLEDAI scores were under control. Our study utilized SLEDAI scores for the categorization of patients because of its practicality and simplicity of use, making it easy to monitor disease status and treatment outcomes.…”