Generic placeholder image

Current HIV Research


ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Research Article

Autoantibodies Among HIV-1 Infected Individuals and the Effect of Anti-Retroviral Therapy (ART) on It

Author(s): Runal John Steve, Diviya Alex, Binesh Lal Yesudhason, John Antony Jude Prakash, Nitty Skariah Mathews, Dolly Daniel, Veena Vadhini Ramalingam, John Paul Demosthenes, Ben Chirag Ghale, Raghavendran Anantharam, Grace Rebekah, Priscilla Rupali, George Mannil Varghese and Rajesh Kannangai*

Volume 19, Issue 3, 2021

Published on: 17 February, 2021

Page: [277 - 285] Pages: 9

DOI: 10.2174/1570162X19666210217120337

Price: $65


Background: Antiretroviral therapy (ART) has led to a decline in autoimmune diseases but lacks studies on its effect on autoantibodies.

Methods: It is a cross-sectional study with archived samples from 100 paired HIV-1 infected ART naïve and experienced individuals and 100 prospectively collected matched blood-donor controls. Antinuclear antibody, IgG anticardiolipin antibody, IgM and IgG β2 glycoprotein-1 antibodies, and total IgG levels were detected. Results are expressed as mean with standard deviation (SD), median, percentage positivity, and a p<0.05 is considered significant. The study was approved by the Institutional Review Board.

Results: The median viral load of the treatment naïve samples was 4.34 Log copies/mL, while all were virally suppressed post ART with a median duration of treatment for 12 months (range: 3-36 months). The percentage of antinuclear antibody positivity was 5% among ART naïve and controls, with a decrease of 2% post ART (p= 0.441). The positivity for anti-cardiolipin antibody was 15% among ART naïve while none of the ART experienced or controls were positive (p<0.05). IgM β2 glycoprotein-1 were 4%, 1% and 3% among ART naïve, treated and controls, respectively (p<0.05). IgG β2 glycoprotein-1 was 2% among ART naïve while none of the treated and controls were positive (p<0.05). The mean total IgG level among ART naïve, experienced, and controls were 21.82 (SD 6.67), 16.91 (SD 3.38), 13.70 (SD 2.24) grams/Litre, respectively (p<0.05).

Conclusion: ART has a significant effect on IgG anti-cardiolipin antibody and total IgG but only a marginal effect on ANA, IgM, and IgG β2 glycoprotein-1 antibodies.

Keywords: Autoantibodies, anti-nuclear antibody (ANA), IgG anti-cardiolipin antibody (aCL), IgM and IgG anti-beta 2 glycoprotein- 1 antibodies (β2 GP1), autoimmunity, HIV-1 infection, antiretroviral therapy, ART naïve and ART experienced.

Graphical Abstract
Goldblatt F, O’Neill SG. Clinical aspects of autoimmune rheumatic diseases. Lancet 2013; 382(9894): 797-808.
[] [PMID: 23993190]
Lesage S, Goodnow CC. Organ-specific autoimmune disease: A deficiency of tolerogenic stimulation. J Exp Med 2001; 194(5): F31-6.
[] [PMID: 11535640]
Iaccarino L, Gatto M, Bettio S, et al. Overlap connective tissue disease syndromes. Autoimmun Rev 2013; 12(3): 363-73.
[] [PMID: 22743033]
Antunes M, Scirè CA, Talarico R, et al. Undifferentiated connective tissue disease: State of the art on clinical practice guidelines. RMD Open 2019; 4: e000786. Available from:
Suurmond J, Diamond B. Autoantibodies in systemic autoimmune diseases: specificity and pathogenicity. J Clin Invest 2015; 125(6): 2194-202.
[] [PMID: 25938780]
Tan EM, Feltkamp TE, Smolen JS, et al. Range of antinuclear antibodies in “healthy” individuals. Arthritis Rheum 1997; 40(9): 1601-11.
[] [PMID: 9324014]
Mackay IR. Tolerance and autoimmunity. West J Med 2001; 174(2): 118-23.
Wahren-Herlenius M, Dörner T. Immunopathogenic mechanisms of systemic autoimmune disease. Lancet 2013; 382(9894): 819-31.
[] [PMID: 23993191]
Rosenblum MD, Remedios KA, Abbas AK. Mechanisms of human autoimmunity. J Clin Invest 2015; 125(6): 2228-33.
[] [PMID: 25893595]
Getts DR, Chastain EML, Terry RL, Miller SD. Virus infection, antiviral immunity, and autoimmunity. Immunol Rev 2013; 255(1): 197-209.
[] [PMID: 23947356]
Ercolini AM, Miller SD. The role of infections in autoimmune disease. Clin Exp Immunol 2009; 155(1): 1-15.
[] [PMID: 19076824]
Smatti MK, Cyprian FS, Nasrallah GK, Al Thani AA, Almishal RO, Yassine HM. Viruses and Autoimmunity: A Review on the Potential Interaction and Molecular Mechanisms. Viruses 2019; 11(8): E762.
[] [PMID: 31430946]
Fujinami RS, von Herrath MG, Christen U, Whitton JL. Molecular mimicry, bystander activation, or viral persistence: Infections and autoimmune disease. Clin Microbiol Rev 2006; 19(1): 80-94.
[] [PMID: 16418524]
Root-Bernstein R. Human Immunodeficiency Virus Proteins Mimic Human T Cell Receptors Inducing Cross-Reactive Antibodies. Int J Mol Sci 2017; 18(10): E2091.
[] [PMID: 28972547]
Jara LJ, Medina G, Saavedra MA. Autoimmune manifestations of infections. Curr Opin Rheumatol 2018; 30(4): 373-9.
[] [PMID: 29528865]
Cainelli F, Betterle C, Vento S. Antinuclear antibodies are common in an infectious environment but do not predict systemic lupus erythematosus. Ann Rheum Dis 2004; 63(12): 1707-8.
[] [PMID: 15547107]
Virot E, Duclos A, Adelaide L, Miailhes P, Hot A, Ferry T, et al. Autoimmune diseases and HIV infection: A cross-sectional study. Medicine (Baltimore) 2017; 96(4): e5769. Available
Iordache L, Launay O, Bouchaud O, et al. Autoimmune diseases in HIV-infected patients: 52 cases and literature review. Autoimmun Rev 2014; 13(8): 850-7.
[] [PMID: 24747058]
Kulthanan K, Jiamton S, Omcharoen V, Linpiyawan R, Ruangpeerakul J, Sivayathorn A. Autoimmune and rheumatic manifestations and antinuclear antibody study in HIV-infected Thai patients. Int J Dermatol 2002; 41(7): 417-22.
[] [PMID: 12121558]
Roussel J, Pandit S, Jordan P, et al. Autoimmune Hepatitis (AIH) in Acquired Immune Deficiency Syndrome (AIDS): A case report and review of literature. Case Reports in Hepatology 2019. Available from:
Filippidis P, Comte D. Autoimmune disorders during chronic human immunodeficiency virus (HIV) infection. Rev Med Suisse 2019; 15(645): 723-31.
[PMID: 30942970]
Yen Y-F, Chuang P-H, Jen I-A, et al. Incidence of autoimmune diseases in a nationwide HIV/AIDS patient cohort in Taiwan, 2000-2012. Ann Rheum Dis 2017; 76(4): 661-5.
[] [PMID: 27590658]
Kaliyadan F. Hiv and lupus erythematosus: a diagnostic dilemma. Indian J Dermatol 2008; 53(2): 80-2.
[] [PMID: 19881993]
Cunha BM, Mota LMH, Pileggi GS, Safe IP, Lacerda MVG. HIV/AIDS and rheumatoid arthritis. Autoimmun Rev 2015; 14(5): 396-400.
[] [PMID: 25578483]
Jian L, Liang W, Zhang Y, et al. Systemic lupus erythematosus patient with false positive results of antibody to HIV: A case report and a comprehensive literature review. Technol Health Care 2015; 23(s1)(Suppl. 1): S99-S103.
[] [PMID: 26410337]
Deas JE, Liu LG, Thompson JJ, et al. Reactivity of sera from systemic lupus erythematosus and Sjögren’s syndrome patients with peptides derived from human immunodeficiency virus p24 capsid antigen. Clin Diagn Lab Immunol 1998; 5(2): 181-5.
[] [PMID: 9521140]
Sánchez-Pardo S, Osorio-Ramírez JA, Choi-Park I, Rojas-Holguín DF, Bolívar-Mejía A, Sánchez-Pardo S, et al. False-positive fourth-generation HIV test associated with autoimmune hemolytic anemia. Case report. Case Rep 2019; 5(2): 132-8.
Marks M, Marks JL. Viral arthritis. Clin Med (Lond) 2016; 16(2): 129-34.
[] [PMID: 27037381]
Christen U, von Herrath MG. Infections and autoimmunity good or bad? J Immunol 2005; 174(12): 7481-6.
[] [PMID: 15944245]
Massabki PS, Accetturi C, Nishie IA, da Silva NP, Sato EI, Andrade LE. Clinical implications of autoantibodies in HIV infection. AIDS 1997; 11(15): 1845-50.
[] [PMID: 9412703]
Muller S, Richalet P, Laurent-Crawford A, et al. Autoantibodies typical of non-organ-specific autoimmune diseases in HIV-seropositive patients. AIDS 1992; 6(9): 933-42.
[] [PMID: 1388904]
Klaassen RJ, Goldschmeding R, Dolman KM, et al. Anti-neutrophil cytoplasmic autoantibodies in patients with symptomatic HIV infection. Clin Exp Immunol 1992; 87(1): 24-30.
[] [PMID: 1733634]
Bijlsma JW, Derksen RW, Huber-Bruning O, Borleffs JC. Does AIDS ‘cure’ rheumatoid arthritis? Ann Rheum Dis 1988; 47(4): 350-1.
[] [PMID: 3365035]
Thompson CG, Gay CL, Kashuba ADM. HIV Persistence in Gut-Associated Lymphoid Tissues: Pharmacological Challenges and Opportunities. AIDS Res Hum Retroviruses 2017; 33(6): 513-23.
[] [PMID: 28398774]
Dandekar S. Pathogenesis of HIV in the gastrointestinal tract. Curr HIV/AIDS Rep 2007; 4(1): 10-5.
[] [PMID: 17338855]
Evidence for link between “leaky gut” and autoantibody production in HIV-positive patients. ScienceDaily 2019. Available from:
Xu W, Luo Z, Alekseyenko AV, Martin L, Wan Z, Ling B, et al. Distinct systemic microbiome and microbial translocation are associated with plasma level of anti-CD4 autoantibody in HIV infection. Sci Rep 2018; 8(1): 12836.
Rawson PM, Molette C, Videtta M, et al. Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection. Nat Med 2007; 13(12): 1431-9.
[] [PMID: 18026114]
Stratton R, Slapak G, Mahungu T, Kinloch-de Loes S. Autoimmunity and HIV. Curr Opin Infect Dis 2009; 22(1): 49-56.
[] [PMID: 19532080]
Swingler S, Zhou J, Swingler C, et al. Evidence for a pathogenic determinant in HIV-1 Nef involved in B cell dysfunction in HIV/AIDS. Cell Host Microbe 2008; 4(1): 63-76.
[] [PMID: 18621011]
Moir S, Fauci AS. B cells in HIV infection and disease. Nat Rev Immunol 2009; 9(4): 235-45.
[] [PMID: 19319142]
Berlin T, Zandman-Goddard G, Blank M, et al. Autoantibodies in nonautoimmune individuals during infections. Ann N Y Acad Sci 2007; 1108: 584-93.
[] [PMID: 17894023]
Burbelo PD, Klimavicz JS, Deeks SG, Kovacs JA, Ragheb JA. Lack of Evidence for Molecular Mimicry in HIV-Infected Subjects. PLoS One 2015; 10(11): e0127662.
[] [PMID: 26599070]
Fernandez SAV, Lobo AZC, Oliveira ZN, Fukumori LMI, P rigo AM, Rivitti EA. Prevalence of antinuclear autoantibodies in the serum of normal blood dornors. Rev Hosp Clin Fac Med Sao Paulo 2003; 58(6): 315-9.
[] [PMID: 14762490]
Wananukul S, Voramethkul W, Kaewopas Y, Hanvivatvong O. Prevalence of positive antinuclear antibodies in healthy children. Asian Pac J Allergy Immunol 2005; 23(2-3): 153-7.
[PMID: 16252846]
Grygiel-Górniak B, Rogacka N, Puszczewicz M. Antinuclear antibodies in healthy people and non-rheumatic diseases - diagnostic and clinical implications. Reumatologia 2018; 56(4): 243-8.
[] [PMID: 30237629]
Pisetsky DS. Antinuclear antibodies in healthy people: the tip of autoimmunity’s iceberg? Arthritis Res Ther 2011; 13(2): 109.
[] [PMID: 21554754]
Rai E, Wakeland EK. Genetic predisposition to autoimmunity--what have we learned? Semin Immunol 2011; 23(2): 67-83.
[] [PMID: 21288738]
Ngo ST, Steyn FJ, McCombe PA. Gender differences in autoimmune disease. Front Neuroendocrinol 2014; 35(3): 347-69.
[] [PMID: 24793874]
Li Q-Z, Karp DR, Quan J, et al. Risk factors for ANA positivity in healthy persons. Arthritis Res Ther 2011; 13(2): R38.
[] [PMID: 21366908]
Hanvivatvong O, Tirawatnapong S, Kaowopas Y, Jitapankul S. Prevalence of autoantibodies in Thai elderly. J Med Assoc Thai 2003; 86(Suppl. 2): S242-9.
[PMID: 12929996]
Andersen-Ranberg K, HØier-Madsen M, Wiik A, Jeune B, Hegedüs L. High prevalence of autoantibodies among Danish centenarians. Clin Exp Immunol 2004; 138(1): 158-63.
[] [PMID: 15373919]
Njemini R, Meyers I, Demanet C, Smitz J, Sosso M, Mets T. The prevalence of autoantibodies in an elderly sub-Saharan African population. Clin Exp Immunol 2002; 127(1): 99-106.
[] [PMID: 11882039]
Watad A, Bragazzi NL, Adawi M, et al. Autoimmunity in the Elderly: Insights from Basic Science and Clinics - A Mini-Review. Gerontology 2017; 63(6): 515-23.
[] [PMID: 28768257]
Vadasz Z, Haj T, Kessel A, Toubi E. Age-related autoimmunity. BMC Med 2013; 11(1): 94.
[] [PMID: 23556986]
Savige JA, Chang L, Horn S, Crowe SM. Anti-nuclear, anti-neutrophil cytoplasmic and anti-glomerular basement membrane antibodies in HIV-infected individuals. Autoimmunity 1994; 18(3): 205-11.
[] [PMID: 7858105]
Sekigawa I, Okada M, Ogasawara H, et al. Lessons from similarities between SLE and HIV infection. J Infect 2002; 44(2): 67-72.
[] [PMID: 12076063]
Kopelman RG, Zolla-Pazner S. Association of human immunodeficiency virus infection and autoimmune phenomena. Am J Med 1988; 84(1): 82-8.
[] [PMID: 3257353]
Promsawan K, Klangsinsirikul P, Dettrairat S, et al. Detection of Antinuclear Antibodies in HIV-Infected Individuals. J Assoc Med Sci 2017; 50(3): 490-0.
Medina-Rodriguez F, Guzman C, Jara LJ, et al. Rheumatic manifestations in human immunodeficiency virus positive and negative individuals: a study of 2 populations with similar risk factors. J Rheumatol 1993; 20(11): 1880-4.
[PMID: 8308773]
Kutty Krishnan K, Rajendran Panchapakesa C, Porkodi R, Madhavan R, Ledge Santh G, Mahesh A. Rheumatological manifestations in HIV positive patients referred to a tertiary care centre. J Indian Rheumatol Assoc 2003; 11: 104-8.
Iordache L, Bengoufa D, Taulera O, et al. Nonorgan-specific autoantibodies in HIV-infected patients in the HAART era. Medicine (Baltimore) 2017; 96(10): e6230.
[] [PMID: 28272216]
Damoiseaux J, von Mühlen CA, Garcia-De La Torre I, et al. International consensus on ANA patterns (ICAP): the bumpy road towards a consensus on reporting ANA results. Auto Immun Highlights 2016; 7(1): 1.
[] [PMID: 26831867]
Sène D, Piette J-C, Cacoub P. Antiphospholipid antibodies, antiphospholipid syndrome and viral infections. Rev Med Interne 2009; 30(2): 135-41.
[] [PMID: 18926604]
Maclean C, Flegg PJ, Kilpatrick DC. Anti-cardiolipin antibodies and HIV infection. Clin Exp Immunol 1990; 81(2): 263-6.
[] [PMID: 2387093]
Petrovas C, Vlachoyiannopoulos PG, Kordossis T, Moutsopoulos HM. Anti-phospholipid antibodies in HIV infection and SLE with or without anti-phospholipid syndrome: Comparisons of phospholipid specificity, avidity and reactivity with beta2-GPI. J Autoimmun 1999; 13(3): 347-55.
[] [PMID: 10550222]
Abdel-Wahab N, Lopez-Olivo MA, Pinto-Patarroyo GP, Suarez-Almazor ME. Systematic review of case reports of antiphospholipid syndrome following infection. Lupus 2016; 25(14): 1520-31.
[] [PMID: 27060064]
Abdel-Wahab N, Talathi S, Lopez-Olivo MA, Suarez-Almazor ME. Risk of developing antiphospholipid antibodies following viral infection: a systematic review and meta-analysis. Lupus 2018; 27(4): 572-83.
[] [PMID: 28945149]
Bundell C, Brunt SJ, Cysique LA, Brusch A, Brew BJ, Price P. The high frequency of autoantibodies in HIV patients declines on antiretroviral therapy. Pathology 2018; 50(3): 313-6.
[] [PMID: 29463387]
Meng Z, Du L, Hu N, et al. Antiretroviral Therapy Normalizes Autoantibody Profile of HIV Patients by Decreasing CD33⁺CD11b⁺HLA-DR⁺ Cells: A Cross-Sectional Study. Medicine (Baltimore) 2016; 95(15): e3285.
[] [PMID: 27082567]
Pereira SA, Antunes AMM, Dias CG, et al. Anti-histone antibodies in HIV-infected patients on Nevirapine-containing antiretroviral therapy. Clin Ther 2015; 37(8): e142.
Baroncelli S, Mezzaroma I, Fantauzzi A, et al. No evidence of autoimmune disorders in antiretroviral-experienced HIV-1-infected individuals after long-term treatment with raltegravir. Antivir Ther 2013; 18(3): 321-7.
[] [PMID: 23047152]
Foulon G, Wislez M, Naccache J-M, et al. Sarcoidosis in HIV-infected patients in the era of highly active antiretroviral therapy. Clin Infect Dis 2004; 38(3): 418-25.
[] [PMID: 14727215]
Silva GAR, Andrade MC, Sugui DdeA, et al. Association between antiretrovirals and thyroid diseases: a cross-sectional study. Arch Endocrinol Metab 2015; 59(2): 116-22.
[] [PMID: 25993673]
Dhasmana DJ, Dheda K, Ravn P, Wilkinson RJ, Meintjes G. Immune reconstitution inflammatory syndrome in HIV-infected patients receiving antiretroviral therapy : Pathogenesis, clinical manifestations and management. Drugs 2008; 68(2): 191-208.
[] [PMID: 18197725]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy