Antinuclear Antibodies (ANA) Test Results with Autoimmune Diseases - Assignment Example

Literature Review: Antinuclear Antibodies (ANA) Test Results with Autoimmune Diseases An autoimmune disease “is characterized by a significantly increased frequency of auto antibodies in significantly increased titres if compared to healthy local controls, matched for sex and age” (Shoenfeld, 1999, p. 24). This occurs when the body immune system mounts an immune attack against its own tissues. Thus, autoimmune diseases are characterized by damage of the affected tissues and inflammation. The exact cause of autoimmune disorders in not clear though most of them have a genetic defect etiology. Antinuclear antibody (ANA) test is used to screen for the presence of autoimmune disorders in patients that have symptoms of an autoimmune reaction. ELISA, enzyme linked immunoabsorbant assay and immunoflourescence microscopy are normally used to perform the test. This paper examines online and print literatures that discuss the use of antinuclear antibody tests in screening for autoimmune diseases. Literature on the legitimacy of ANA test Bonaguri et al. (2011) conducted a study describing joint laboratory clinics guideline for reducing clinically inappropriate requests for ANA tests in a broad geographical area (Parma, Modena, Piacenza and Reggio-Emilia) for the diagnosis of autoimmune, rheumatic disease. The researchers conducted an observational research that compared a number of ANA tests, anti-dsDNA and anti-ENA, as well as positive test results before and after the establishment of diagnostic algorithm in hospitalized patients. A joint guideline for auto antibody testing that placed ANA at the first level was inexistence since January 2009. The researcher analyzed results that were carried in 2008 and 2009. The study’s result showed a significant reduction in the percentage of anti-dsDNA and anti-ENA tests. In addition, the study revealed an increase in the second level tests positivity of ENA and anti-dsDNA after the implementation of the protocol. The study is essential because it shades light on the topic under study by illustrating diagnostic protocols involved in ANA. Tonutti et al. (2004) had a similar approach. Tonutti et al. (2004, p. 171) aimed at “evaluating the diagnostic accuracy of five commercially available enzyme immunoassay kits for ANA detection and to verify the possibility of using them as an alternative to the IIF method”. The study involved two groups; one group had participants without any autoimmune disease while the other group had patients with autoimmune disease. Sera was collected fro both groups, and ANA performed using IIF and the five enzyme assay kits. The results were varied. The kits showed different levels of sensitivity and accuracy. Some of them were more accurate and sensitive than IIF. On the other hand, some kits posted inaccurate results. The researchers suggested that “there should be a careful evaluation of the various kits on the market before using them in ANA tests” (Tonutti et al., 2004, p.179). In addition, Wang et al. (2011, p. 222) study aimed at clarifying the relationship between initial presentations, ANA titre and final diagnoses. The researchers collected data from patients who visited National Taiwan University Hospital to undertake their first ever ANA tests. The researchers analyzed the ANA tests, symptoms during the test, and final diagnoses. They observed the enrolled patients for a period of six months. The researchers found out that most patients who came for ANA test had joint pains at the time of testing. Those with high ANA titres showed a high chance of testing positive for autoimmune disorders. In addition, patients with joint pain, fever, abnormal urinalysis and skin rash presented high ANA titres. Anti double strand DNA antibodies together with anti extractable nuclear antibodies occurred in high concentrations in patients with high ANA titres. The study found out that high titre is a biomarker for autoimmune disorders most importantly in patients with joint pain, fever, abnormal urinalysis and skin rash. This study is exceptionally vital to the topic of study because it illustrates possible biomarkers and symptoms of autoimmune diseases. Studies that aimed at comparing diagnostic assays used in ANA Mariz et al. (2011, p. 191) study endeavored “to identify features of ANA-HEp-2-test results that discriminate ANA positive, healthy individuals and patients with autoimmune rheumatic diseases (ARDs)”. Data from 918 healthy individuals and 153 patients with ARDs following clinical assessment was analyzed. Health individuals who tested positively for ANA were observed for a period of 3-5 years. After an in depth analysis of the results, the researchers concluded that titres and patterns on ANA-HEp-2-test significantly enhance the ability of clinicians to differentiate ANA positive, healthy individuals from individuals with ARDs. The study offers a powerful ARD diagnostic tool thus enhances the comprehension of the topic under study. Wieser, Pohla-Gubo and Hintner, argue that the diagnostic value of ANA must be defined by its correlation to the clinical situation of each patient. The authors note that clinicians often fail to correlate clinical features and laboratory results. For that matter, the researchers examined three reports that had two contrasting scenarios. In the first scenario, presence of a low antibody titer could not predict the rapidly fatal outcome. In the second scenario, high positive titres of ANA were observed in patients with mild a definite mild course. These differences have led to the establishment of various ANA screening algorithms depending on the age, suspected autoimmune and screening results. Good examples of such two tests include the cobra core HEp2 enzyme immunoassay (CC-ANA-EIA) and indirect immunoflourescence (IIF). The researchers conducted a study to compare these two tests. Their findings indicated that neither of the two tests guarantees 100% sensitivity. In addition, they noted that both tests are reliable and comparable for testing patents that have diagnosis or suspected to have SLE. They note that the clinician should have a detailed evaluation of the nature of the disease because this will assist in determining the next course of treatment. The study enhances the comparison of the two tests. Gonzalez et al note immunoflourescence assay has been the standard method for ANAs. This has led to the development of generic solid enzyme immunoassay in a bid to standardize and simplify immunoflourescence assay. For that matter, the researchers conducted a study in order to evaluate the clinical significance of the two tests and how they are related. The researchers learnt that sensitivity, specificity and characteristics of COBAS Core ANA from SLE and other systemic and non systemic autoimmune disorders make it an inadequate automated method for ANA screening. Dipti et al acknowledge the fact that SLE is a multisystem, chronic and episodic autoimmune disorder that is characterized by the presence of ANA. The researchers also note that indirect immunoflourescence (ANA-IFA) and enzyme immunoassay (ANA-EIA) are most commonly used tests. The researcher conducted a study to compare the sensitivity of the two tests. Their findings indicated that ANA-IFA had 100% sensitivity while ANA-EIA had 55% sensitivity. The researchers recommended that ANA-IFA should be used to detect ANA in children with SLE because it is superior to ANA-EIA. Kim, Y., Park, Lee and Kim, S., conducted a study to compare two ABA assays. A newly developed a totally automated Luminex based assay (BioPlex Tm 2200 system); can detect various auto antibodies simultaneously from a single sample. The researchers compared BioPlex Tm 2200 system with ELISA. The researchers found out that BioPlex Tm 2200 system produced results which were comparable with those produced by convectional ELISA for detecting auto antibodies. BioPlex Tm 2200 system also measured multifarious auto antibodies concurrently in a single sample. The researchers recommended the use of BioPlex Tm 2200 system in clinical laboratories for screening autoimmune diseases. Charlotte et al. endeavored to evaluate and compare the accuracy of three enzyme immunoassays and a double radial immunodiffusion test in addition to immunoflourescence microscopy for routine ANA laboratory screening. The authors noted that different ANA tests reflect different aspects of the analyzed auto antibodies. They also stated that the ANA testing relies significantly on IF microscopy and precipitin tests. Thus, they recommended that IF microscopy should remain the gold standard for testing SLE and other autoimmune diseases until all the diagnostic and classification criteria for SLE and other autoimmune disorders have been revised. Shovman et al endeavored to determinate ANA and other auto antibodies to the nine extractable nuclear antigens by the AtheNA Multi Lyte ANA system and compare the results produced by this method to the commonly used enzyme immunoassays. The researchers found out that AtheNA Multi Lyte ANA system may be an essential diagnostic tool for ANA screening. However, additional investigations are required to compare an analytical performance between AtheNA and the common methods in the determination of an individual’s profile. Xu et al endeavored to determine whether multiplex ANA can replace IFA in pediatric patients. The researchers used archived frozen samples from patients with suspected autoimmune diseases. The collected samples had previously undergone ANA testing using IFA methodology. The researchers learnt that multiplex ANA technique is a reliable method for detecting antinuclear antibodies. However, it cannot replace IFA as ANA screening in pediatric population especially for children with idiopathic arthritis. In another study Shankar, Ramnane, Rajouria and Eliz (2010) conducted a study to evaluate the types of chronic urticaria with reference to etiology history and investigation. Urticaria may be chronic or acute. The researchers studied 150 patients with chronic urticaria for a period of six weeks. Autologous serum skin tests (ASST) were conducted after ruling out a possibility of physical urticarias. The researchers conducted other necessary tests like skin prick tests and battery tests. The researchers found out that “more than half of the patients had chronic autoimmune urticaria on the basis of ASST” (Shankar et al., 2010, p. 38). A good number of the patients had had serological biomarkers of autoimmune reactions. The researchers argued that ASST offers a cheap and straight forward way of checking chronic urticaria thus enabling the clinician to concentrate on underlying systemic autoimmune disease. The study is essential because it gives a clarification on the diagnosis of an exemplified autoimmune disease (chronic urticaria). Moreover, De-Beeck et al. noted that solid phase assay are on the increase and may replace direct immunoflourescence during an ANA test. The researchers aimed at comparing solid phase assay to indirect immunoflourescence during an ANA test. The researchers used three groups of patients. The first group consisted of patients with an autoimmune of the connective tissue, the second had healthy blood donors, the third had patients with chronic fatigues symptoms and the last category was a control group. Solid phase assay (EliA CTD) screen for SLE, systemic Sclerosis, primary Sjogren’s disease, MCTD and inflammatory myopathy produced a sensitivity of 74%, 72%, 89%, 100% and 39% respectively. The reactivity in control group, blood donors and patients with chronic fatigue was less than 4%. The researchers noted that a positive, solid assay test indicated a higher chance of systemic rheumatic disease than a positive test result posted by indirect immunoflourescence. Thus, the researchers concluded that a negative predictive value is higher in indirect immunoflourescence assay than in solid assay test (EliA CTD). However, Reen et al. (2010, p. 345) study endeavored to clarify “whether occupational and environmental conditions other than mercury exposure associated with artisanal gold mining affect the prevalence of markers of autoimmune dysfunction”. Their study was based on the scientific fact that mercury is an immunotoxic substance capable of inducing autoimmune reactions. The researchers analyzed ANA, antinuclear auto antibodies (ANoA) and cytokine concentrations in serum of collected from artisans from mercury exposed gold mines and diamond exposed mines. The researchers discovered that miners from mercury exposed gold mines had high ANA prevalence and titres when compared to their counterparts working in diamond mines. In addition, miners from mercury exposed Gold mines had high pro-inflammatory cytokine serum concentrations. Thus, the study concluded that mercury is a potential risk factor for auto immune reactions and systemic inflammation. This study provides a different view of ANA application. Literature on the use of ANA test in Children Dipti, Azam, Sattar and Rahman (2012) endeavored to detect ANA immunoflourescence assay using HEp-2 cell substrate and enzyme, immune assay in children with SLE, and to offer a comparison of the two techniques. The two techniques compared were indirect immunoflourescence (ANA-IFA) and Enzyme immunoassay (ANA-EIA). The researchers used cross sectional analysis. The researchers had a group of 20 participants with childhood SLE and another group of 20 participants without SLE but with other rheumatic disorders. In the SLE group, ANA- IFA posted 100% positive result while ANA –EIA posted a positivity of 55%. It was noted that the sensitivity of ANA-IFA was 100% while that of ANA-EIA was 55%. They concluded that ANA-IFA is more reliable than ANA-EIA in detecting SLE in children. They recommended that ANA-IFA should be requested as a primary screening test for children presenting signs of SLE. Malleson, Mackinnon, Sailer-Hoeck, and Spencer (2010) also based their research on children. Malleson, Mackinnon, Sailer-Hoeck, and Spencer (2010) based their study on the fact that ANA test is overused in pediatrics. Research has shown that ANA has a role in serologic testing, but “it should be a limited one” (Malleson et al., 2010, p. 35). The test is requested in suspicion of rheumatic illnesses in primary care settings. The test has low specificity and sensitivity when it is used to screen for musculoskeletal and rheumatic illnesses in children. Experts suggest that it may be ordered in non specific complaints like musculoskeletal pain. It is useful in screening for SLE, MCTD and overlapping autoimmune reactions in children. The test should be requested in cases when children have shown definitive signs of the above conditions. The study conducted by Malleson et al. aimed at providing data that support the above facts. They argue that primary health providers need to limit ANA testing. This will prevent parental anxieties, unnecessary venipuncture pain, extra medical expenses and unnecessary referrals. Thus, primary care providers should order for ANA test only when children present definitive symptoms. In addition, they suggested that in case ANA was requested and the titres are extremely low; the result can be ignored so long as the child does not present features of a systemic illness. The study is particularly helpful to my current topic because it is an analysis of various literatures on the topic under study. McGhee, Kickingbird and Jarvis conducted a study to determine the clinical utility of ANA tests in screening children for rheumatic diseases. The researchers also wanted to find out whether there are specific signs and symptoms that enhance the clinical utility of ANA tests in children. The researchers note that ANA tests are frequently used to screen chronic inflammatory diseases such as SLE in children. Malleson et al argue ANA is overused in children. They also argue that this test is exceptionally useful in serology but it should have a limited role. According to Malleson et al, ANA are often ordered when screening for rheumatic illnesses in a primary care setting. The researchers recommend that ANA should be ordered when necessary for it to provide meaningful results. The diagnostic utility of this test however is limited because of the large number of who have low titre of positive tests. Their study illustrated that age and ANA titre assist in discriminating children with SLE from children with other conditions. They also noted that ANA tests are of no diagnostic utility in either making or excluding the diagnosis of Juvenile rheumatoid arthritis. In addition, Torok and Arkachaisri (2010, p. 15) conducted a study “to determine the frequency of thyroid antibodies in children referred to pediatric rheumatology center for a positive ANA without evidence of connective tissue disease”. The researchers used a retrospective chart review to analyze data collected between 2003 and 2008 from affected children. The researchers learnt that thyroid antibodies associated with chronic lymphocytic thyroiditis, Anti-Thyroglobulin (ATG) and anti thyroid peroxidase (ATPO) occurred in higher concentrations in ANA positive children, without rheumatologic condition when compared to the general pediatric population. ANA pattern and titre were not helpful in determining the presence or absence of thyroid antibodies. Thus, the researchers recommended “routine evaluation of ATG and ATPO with thyroid function tests in ANA positive pediatrics” (Torok & Arkachaisri, 2010, p. 18). The study is essential because it shades light on the ANA diagnostic procedures in children. Literature on the use of ANA test in various disorders Zhang, Wang, B. and Wang, T. argue de novo autoimmune hepatitis A (AIH) occurs in patients that undergo liver transplantation for different etiology. In their study, the researchers examined a 55 year old woman who underwent liver transplantation due to PCB. A year later, the woman complained of excessive fatigue. On examination, she was found to have elevated serum alanine transaminases, globulin. She also tested positive for ANA. However, the patient recovered fully after the administration of proper medication. Their steady provide a good correlation between liver transplantation and AIH. The study provides significant findings that will enhance my understanding of the topic at hand. Marzo-Ortega et al conducted a study to determine the prevalence of ANA, antineutrophil cytoplasmic antibodies (ANCA) and new autoimmune syndrome in (Microcycline) MN exposed and unexposed population with acne. Marzo-Ortega based their study on the findings of previous studies that indicated MN is one of the commonly prescribed therapies for acne and it is known to autoimmune disorder including drug induced lupus. Tamer et al acknowledge the fact that salivary and lachrymal glands dysfunction is relatively frequent after radioiodine therapy. Previous studies have reported an association between Sjogren’s syndrome (SS) and other autoimmune rheumatic diseases as fibromyalgia syndrome (FMS). Previous studies have reported that thyroid autoimmunity is high in FMS patients when compared t other subjects. On the other hand, Gilburd et al note that flow based, multiplex bead arrays have been formulated for numerous applications including the detection of antibodies to extractable nuclear antigens. This technique offers a rapid sensitive method to evaluate multiple analyses in a single tube. Thus, Gilburd et al conducted a study determine whether Athena multi Lyte test system utilizes Luminex corporation’s MBA technology for the identification of ANA and ENA antibodies in the sera of participants with Sjogren’s syndrome and in healthy individuals. The researchers noted that Athena multi Lyte test system offers a sensitive and a specific result for the detection of ANA and ENA antibodies in the blood samples of patients with SS. Tamer et al endeavored to detect the occurrence of SS and any rheumatologic association in cancer thyroid patients after radioiodine therapy and evaluate the salivary and lachrymal glands function. The researchers found out that after radioiodine therapy, assessment and follow up of salivary and lachrymal glands is necessary. They also noted that abnormal levels of anti-Ro and Anti-La increase the risk for SS that should be closely monitored and FMS is a common association. El-Kabarity R. and El-Kabarity, H. conducted a study to assess the diagnostic reliability of serum anti shock protein 70 (anti-HSP70). The study involved 43 participants with idiopathic sensorineural hearing loss. The study indicated that individuals with idiopathic sensorineural hearing loss can benefit from testing serum anti-HSP70 shortly after the onset of symptoms. The study illustrated an autoimmune disease that can be detected by testing anti-HSP70. Alitintas et al argue there is an increased risk of lymphoma subsequent to autoimmune conditions. They note that autoimmune disorders may occur in the course of lymphomas. Thus, they conducted a study to evaluate the relationship between autoimmunity and related auto antibodies in patients with non Hodgkin’s and Hodgkin’s Lymphoma. The researchers learnt that ANA related auto antibodies can frequently be detected during lymphoma treatment. The study further illustrated that the majority of lymphoma patients with positive ANAs did not present autoimmune diseases. Thus, the study demonstrated the lack of a correlation between the presence of ANA and auto immune diseases. Kulthanan et al based their study on the findings of previous studies that indicated that human HIV is associated with autoimmune and rheumatic diseases. Thus, they conducted a study to assess autoimmune and rheumatic manifestations in HIV infested patients and their correlation with ANA tests. The researchers noted that autoimmune and rheumatic manifestations were not uncommonly manifested in HIV infested patients. They also noted that HIV infection may sometimes mimic SLE. In another study, Aksu et al argue that the detection of ANA is a diagnostic adjunct of in individuals with suspected autoimmune connective tissue diseases, and various detection methods are in use. Thus, the researchers conducted a study to analyze the agreement between ANA-IF and immunoblotting (IB), and determine a cut off for children subjects in a laboratory setting. The study indicated that ANA-If was the superior method. In addition, Rubin et al argue that ANA test has been widely used to test autoimmune diseases, but its value for diagnostic purposes is compromised by a low specificity and high prevalence in disease free individuals. The researchers also indicate that the capacity of auto antibodies to fix serum complement proteins when bound to antigens is an essential effector function because this property is associated with acute and inflammatory processes. Rubin’s study found out the measurement of that Complement fixing auto antibodies is an important diagnostic tool and may have immunopathologic implications. Seo et al based their study on recent findings that indicate that ANAs are frequently detected in patients with acute hepatitis A. However, the clinical significance of ANA remains uncertain. Thus, the researchers conducted this study to evaluate the significance of ANA tests in patients with acute hepatitis A. The researchers recruited participants from admitted patients with acute Hepatitis A. ANA tests were then conducted on these patients. According to their findings, ANAs were frequently and transiently detected in patients with acute hepatitis A. However, the clinical outcome of ANAs could not be correlated with the clinical outcome of acute hepatitis A. The study shades light on the cases that ANA test might not be relevant. Literature review on the use of ANA test in other Subjects Hansson-Hamlin, Lilliehook and Trowald-Wigh note that autoimmune diseases in dogs are known as Systemic Lupus Erythematosus (SLE), with a positive ANA test as a hallmark. In human subjects, other ANA positive disorders with overlapping diagnostic features are present. The researchers conducted a study to elucidate whether different patterns of ANA represent different patterns of autoimmune diseases in dogs. The researchers found out those dogs with homogenous IIF-ANA, SLE might be the probable diagnosis because of the diversity of clinical manifestation and auto body reactivity against chromosomal antigens. This study necessitates the comparison of ANA tests in humans and dogs This paper has examined literatures from various online and print data bases that offer vital information on the use of ANA test in screening for autoimmune diseases. All the literatures are current thus they provide the latest information on this topic. The literatures will be very helpful in assisting me to understand the topic under study. References Aksu, G., Gulez, N., AZarsiz, E., Karaka, N., and Kutukculer, N. (2010). Determination of Cut- Off Titers and Agreement Between Immunofluorescence and Immunoblotting Methods for Detecting Antinuclear Antibodies in Children. Journal of Clinical Laboratory Analysis, 24(4). Altintas, A., Cul, T., Pasa, S., Danis, R., Kilinc, I., Ayyildiz, O., and Muftuoglu E. (2008). Clinical significance of elevated antinuclear antibody test in patients with Hodgkin's and Non-Hodgkin's lymphoma: a single center experience. Minerva Medica , 99(1) 7-14. Bonaguri, C., et al. (2011). Italian multicentre study for application of a diagnostic algorithm in autoantibody testing for autoimmune rheumatic disease: Conclusive results. Autoimmunity Reviews, DOI. 10.1016/j.autrev.2011.06.006. Charlotte, D., Skogh, T., Aberg., A., Jalal, A., and Olcen, P. (2004). Methods of choice for diagnostic antinuclear antibody (ANA) screening. Benefit of adding antigen-specific assays to immunofluorescence microscopy. Journal of Autoimmunity, 22(3), 241-248. De-Beeck, K., et al. (2011). Detection of antinuclear antibodies by indirect immunofluorescence and by solid phase assay. Autoimmunity Reviews, 10(12), 801-808. Dipti, T., Azam,M., Sattar, M. and Rahman, S. (2012). Detection of anti-nuclear antibody by immunofluorescence assay and enzyme immunoassay in childhood systemic lupus erythematosus: experience from Bangladesh. International Journal of Rheumatic Diseases, 15 (1), 121-125. El-Kabarity, R., and El-Kabarity , H. (2011). Diagnostic Value of Serum Anti-Heat Shock Protein 70 (Anti-HSP70) in Cases of Autoimmune Inner Ear Disease. Journal of International Advanced Otology, 7(1), 55-61. Gilburd, B., Abu-Shakra, M., Mahmoud, S., Goiordano, A., Bocci, B., Monache,D., and Gerl, R. (2004). Autoantibodies Profile in the Sera of Patients with Sjogren's Syndrome: The ANA Evaluation--A Homogeneous, Multiplexed System. Clinical & Developmental Immunology, 11(1), 53-56. Gonzalez, C., Inmaculada, A., Monserrat, H., Navajo, J., and Manuel, J. (2002). Antinuclear antibodies (ANA) screening by enzyme immunoassay with nuclear HEp-2 cell extract and recombinant antigens: analytical and clinical evaluation. Clinical Biochemistry, 35(6), 463-469. Hansson-Hamlin, H., Lilliehook, I., and Trowald-Wigh, G. (2006). Subgroups of canine antinuclear antibodies in relation to laboratory and clinical findings in immune-mediated disease. American Society For Veterinary Clinical Pathology, 35(4), 397-404. Kim, Y., Park, Y., Lee, Y., Kim, S. (2012). Comparison of automated multiplexed bead-based ANA screening assay with ELISA for detecting five common anti-extractable nuclear antigens and anti-dsDNA in systemic rheumatic diseases. Clinica Chemica Acta, 413 (1/2), 308-311. Kulthanan, K., Jameton, S., Omcharoen, V., Linpiyawan, R., Ruangpeerakul, J., and Sivayathorn, A. (2002). Autoimmune and rheumatic manifestations and antinuclear antibody study in HIV-infected Thai patients. International Journal of Dermatology, 41(7). MacGhee, J., LKickingbird, L., and Jarvis, J., (2004). Clinical utility of antinuclear antibody tests in children. BMC Pediatrics, 9(4), 4-133. Malleson, P., Mackinnon, M., Sailer-Hoeck,M. and Spencer, C. (2010). Review for the generalist: The antinuclearantibody test in children - When to use it andwhat to do with a positive titer. Pediatric Rheumatolog, 8, 27-32. Mariz, H., Sato, E., Barbosa, S.,Rodrigues, S. Dellavance,A. and Andrade, L. (2011). Pattern on the Antinuclear Antibody-HEp-2 Test Is a Critical Parameter for Discriminating Antinuclear Antibody-Positive Healthy Individuals and Patients With Autoimmune Rheumatic Diseases. Arthritis and Rhumatism, 63(1), 191-200. Marzo –Ortega, H., Baxter, K., Strauss , R., Drydale, S., Griffiths, B., et al. (2007). Is minocycline therapy in acne associated with antineutrophil cytoplasmic antibody positivity? A cross-sectional study. British Journal of Dermatology, 156(5), 1005-1009. Reen, M., et al. (2010). Mercury exposure, serum antinuclear/antinucleolar antibodies, and serum cytokine levels in mining populations in Amazonian Brazil: A cross-sectional study. Environmental Research , 10(4):345-354. Rubin, L., Teodorescu., Beutner, H., and Plunkett, R. (2004). Complement-fixing properties of antinuclear antibodies distinguish drug-induced lupus from systemic lupus erythematosus. Lupus,13(4). Seo, Y., Lee, K., Jung, E, Ann, H., Ki, J. et al. (2011). Clinical Significance of the Detection of Antinuclear Antibodies in Patients with Acute Hepatitis A. Gut and Liver , 5 (3) 340-347. Shankar, D., Ramnane, M., Rajaouria, M. and Eliz, A . (2010). Etiological Approach to Chronic Urticaria. Indian Journal of Dermatology, 55(1), 33-38. Shoenfeld, Y. (1999). The Decade of Autoimmunity. Amsterdam: Elsevier. Shovman, O., Gilburd, B., Zandman, Goddard, G., Langevitz, P., and Shoenfeld, Y.(2005). Multiplexed AtheNA multi-lyte immunoassay for ANA screening in autoimmune diseases. Autoimmunity, 38(1), 105-109. Tamer, G. , Samar, M., Ahmed, A., and Hossam, K. (2011). Original Article: Sjögren syndrome and fibromyalgia after radioiodine therapy in cancer thyroid patients. The Egyptian Rheumatologist, 33(2), 107-112. Tonutti, E., et al. (2004). Diagnostic Accuracy of Elisa Methods as an Alternative Screening Test to Indirect Immunofluorescence for the Detection of Antinuclear Antibodies. Evaluation of Five Commercial Kits. Autoimmunity, 37(2), 171-176. Torok, K. and Arkachaisri, T. (2010). Autoimmune thyroiditis in antinuclear antibody positive children without rheumatologic diseas. Pediatric Rheumatology, 8, 15-18. DOI: 10.1186/1546-0096-8-15. Wang, K. et al. (2011). The initial manifestations and final diagnosis of patients with high and low titers of antinuclear antibodies after 6 months of follow-up. Journal of Microbiology, Immunology and Infection, 44(3), 222-228. Wieser, M., Pohla-Gubo, G., and Hintner, H. (2001). Review: Antinuclear antibodies (ANA) Diagnostic value of different methods for screening and differentiation. Clinical and Applied Immunology Reviews, 1(3) 201-206. Xu, M., Roberts, B., Busby, B., Jack, R ., Finn, L., and Emery, H. (2007). Evaluation of Multiplex Antinuclear Antibody Assay in Pediatric Patients. Laboratory Medicine, 38(11), 671-675. Zhang, Y., Wang, B., and Wang,T. (2010). De Novo Autoimmune Hepatitis With Centrilobular Necrosis Following Liver Transplantation for Primary Biliary Cirrhosis: A Case Report. Transpalntation Proceedings, 42(9), 3854-3857. Read More