Viral infection and reactivation in autoimmune disease

Chakravarty, Eliza F.

doi:10.1002/art.23883

Cited by 27 publications

(22 citation statements)

References 76 publications

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“…The bidirectional paradigm of autoimmunity and infections Patients with ADs have at least a twofold risk of acquiring infections compared with healthy individuals [22]. Box 1.…”

Section: Manifestation Of Autoimmune Diseases and Infectionsmentioning

confidence: 99%

Infections and autoimmunity – friends or foes?

Kivity

Agmon‐Levin

Blank

et al. 2009

Trends in Immunology

356

289

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“…The bidirectional paradigm of autoimmunity and infections Patients with ADs have at least a twofold risk of acquiring infections compared with healthy individuals [22]. Box 1.…”

Section: Manifestation Of Autoimmune Diseases and Infectionsmentioning

confidence: 99%

Infections and autoimmunity – friends or foes?

Kivity

Agmon‐Levin

Blank

et al. 2009

Trends in Immunology

356

289

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“…Several studies have shown that HZ is more common and can present with more severe manifestations among patients with systemic lupus erythematosus (SLE) [2–12]. Some studies suggest that the incidence may be increased in SLE even in the absence of immunosuppressive medications [3,9] and during periods of relative disease quiescence [13], possibly because of an inherent deficiency in cell mediated immunity associated with the disease process itself.…”

Section: Introductionmentioning

confidence: 99%

Herpes Zoster Vaccination in SLE: A Pilot Study of Immunogenicity

Guthridge

Cogman²,

Merrill³

et al. 2013

J Rheumatol

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Background Patients with systemic lupus erythematosus (SLE) are at increased risk of herpes zoster (HZ). Although a vaccine for HZ has been FDA approved, its use in immunocompromised individuals remains controversial because it is a live-attenuated virus vaccine. We performed a pilot study of the immunogenicity of Zostavax® in SLE patients. Methods Ten SLE patients and 10 controls ≥50 years old participated in this open label vaccination study. All were seropositive for varicella zoster virus (VZV). SLE patients were excluded for SLEDAI>4, use of mycophenolatemofetil, cyclophosphamide, biologics, or >10 mg prednisone daily. Follow-up visits occurred at 2, 6, and 12 weeks. Clinical outcomes included the development of adverse events, particularly HZ or vesicular lesions, and SLE flare. Immunogenicity was assessed with VZV-specific IFN-γ producing ELISPOT assays and with antibody concentrations. Results All subjects were women. SLE patients were slightly older than controls (60.5 vs. 55.3 years, p<0.05) Median baseline SLEDAI was 0 (range 0–2) for SLE patients. No episodes of HZ, vesicular rash, serious adverse events, or SLE flares occurred. Three injection site reactions occurred in each group: mild erythema or tenderness. The proportion of subjects with a >50% increase in ELISPOT results following vaccination was comparable between both groups, although absolute SLE responses were lower than controls. Antibody titers increased only among controls following vaccination (p<0.05). Conclusions Zostavax vaccination yielded a measurable immuneresponse in this cohort of mild SLE patients on mild-moderate immunosuppressive medications. No herpetiform lesions or lupus flares were seen in this small cohort of patients.

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“…11,12 While effective at reducing inflammation, these chronic treatments have undesirable side effects and reduce overall immunity (i.e., immunosuppression), leading to increased risk for infections and cancer. 13–15 Thus, novel therapeutic approaches to lupus are greatly needed. Toward this end, we began a program to target specific autoantibody populations with small-molecule “decoy antigen” compounds, thereby rendering them unavailable to bind tissue antigen.…”

Section: Introductionmentioning

confidence: 99%

Amending HIV Drugs: A Novel Small-Molecule Approach To Target Lupus Anti-DNA Antibodies

VanPatten

Sun

et al. 2016

J. Med. Chem.

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Systemic lupus erythematosus is an autoimmune disease that can affect numerous tissues and is characterized by the production of nuclear antigen-directed autoantibodies (e.g., anti-dsDNA). Using a combination of virtual and ELISA-based screens, we made the intriguing discovery that several HIV-protease inhibitors can function as decoy antigens to specifically inhibit the binding of anti-dsDNA antibodies to target antigens such as dsDNA and pentapeptide DWEYS. Computational modeling revealed that HIV-protease inhibitors comprised structural features present in DWEYS and predicted that analogues containing more flexible backbones would possess preferred binding characteristics. To address this, we reduced the internal amide backbone to improve flexibility, producing new small-molecule decoy antigens, which neutralize anti-dsDNA antibodies in vitro, in situ, and in vivo. Pharmacokinetic and SLE model studies demonstrated that peptidomimetic FISLE-412,1 a reduced HIV protease inhibitor analogue, was well-tolerated, altered serum reactivity to DWEYS, reduced glomeruli IgG deposition, preserved kidney histology, and delayed SLE onset in NZB/W F1 mice.

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Viral infection and reactivation in autoimmune disease

Cited by 27 publications

References 76 publications

Infections and autoimmunity – friends or foes?

Infections and autoimmunity – friends or foes?

Herpes Zoster Vaccination in SLE: A Pilot Study of Immunogenicity

Amending HIV Drugs: A Novel Small-Molecule Approach To Target Lupus Anti-DNA Antibodies

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