A2Ar-dependent PD-1+ and TIGIT+ Treg cells have distinct homing requirements to suppress autoimmune uveitis in mice.

The proper function of regulatory T cells (Tregs) to suppress inflammation requires homing to the correct tissue site. Resolution of autoimmune uveitis generates distinct programmed death receptor 1 (PD-1+) and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT+) Tregs in an adenosine 2A receptor (A2Ar)-dependent manner found in the spleen. Where and how these Tregs migrate from the spleen to prevent uveitis is not known. In this work, we show that A2Ar-dependent Tregs migrated to the eye and secondary lymphoid tissue and expressed chemokine receptor (CCR)6 and CCR7. Suppression of autoimmune uveitis required CCR6 and CCR7 expression for TIGIT+ Tregs but not PD-1+ Tregs. Moreover, stimulation of A2Ar on T cells from patients showed a decreased capacity to induce TIGIT+ Tregs that expressed CCR6 or CCR7, and PD-1+ Treg that expressed CCR6. This work provides a mechanistic understanding of the homing requirements of each of these Treg populations. Importantly, this work is clinically relevant because patients with chronic autoimmune uveitis are unable to induce the Treg populations identified in mice that home to the target tissue.

Long-term remission of ocular cicatricial pemphigoid off immunomodulatory therapy.

PURPOSE: To evaluate whether long-term remission of ocular cicatricial pemphigoid (OCP) after withdrawal of immunomodulatory therapy (IMT) is possible. METHODS: A total of 34 of 464 presenting patients (66 eyes) with biopsy-proven OCP in long-term remission off IMT were identified after finishing a 2-year IMT regimen without active disease (2005-2015). Long-term remission off IMT for OCP was defined as patients withdrawn from IMT ≥1 year lacking clinically detectable progressive scarring according to Foster staging and subjective assessment. RESULTS: All 34 patients achieved ≥1 year of clinical remission without IMT following 2 years IMT lacking active disease. Mean onset age of OCP was 67.0 years, and median follow-up time was 63.4 months. Mean duration between OCP onset and IMT initiation was 29.5 months, with a mean sustained remission time of 36.0 months off IMT. The mean duration of IMT prior to remission off IMT was 34.8 months (median 32 months, IQR 27-39.5 months). Commonly, methotrexate was used prior to OCP remission (19 patients; 55.9%). Two patients experienced mild flare-up postremission off IMT at months 25 and 37 and a course of topical steroid appeared to resolve the inflammation. Another patient had active inflammation at last office visit 5 years after discontinuation of IMT and will restart IMT. CONCLUSIONS: Long-term remission for OCP off IMT may be achieved after stepladder IMT is implemented and withdrawn. Longer follow-up and more sensitive measures of scarring and inflammation are needed to generate a consensus on the definition of complete remission and on cessation of systemic IMT for OCP.

Recurrent conjunctivitis and scleritis secondary to coexistent conjunctival pemiphigus vulgaris and cryptic herpes simplex infection: a case report.

PURPOSE: To report recurrent conjunctivitis and scleritis secondary to coexistent conjunctival pemiphigus vulgaris and cryptic herpes simplex infection. DESIGN: Case report. METHODS: Retrospective review. RESULTS: A 54-year-old woman presented with recurrent left eye irritation and redness. Four years earlier, she was diagnosed (biopsy) with cutaneous pemphigus vulgaris requiring immunomodulatory therapies. She was receiving oral acyclovir for recurrent genital herpes and intravenous immunoglobulin for pemphigus. Examination revealed unilateral necrotizing scleritis and conjunctivitis. Immunohistochemical staining of biopsies demonstrated conjunctival pemphigus and herpes in conjunctiva and sclera. Valacyclovir therapy brought resolution. CONCLUSION: Cryptic ocular herpes may confound matters in someone with an autoimmune disease thought to be the sole source of ocular inflammation. Immunohistochemical analysis can resolve the mystery.

Adverse drug reactions to treatments for ocular toxoplasmosis: a retrospective chart review.

OBJECTIVE: This study evaluated the incidence and types of adverse drug reactions (ADRs) associated with medications used to treat active toxoplasmic chorioretinitis. METHODS: This was a retrospective review of the clinical records of a consecutive series of patients with active toxoplasmic chorioretinitis, examined between March 1991 and August 1998. For inclusion in the review, patients had to have been diagnosed with active toxoplasmic chorioretinitis, been treated with a single drug or drug combination indicated for this condition, and been followed for at least 8 weeks. Patients who were lost to follow-up or who had incomplete chart data were excluded. Demographic data, pertinent aspects of the medical history, drug treatments, and ADRs associated with antitoxoplasmic treatment were recorded. RESULTS: Fifty-five patients met the criteria for inclusion in the review. In descending order of frequency, they received antitoxoplasmic treatment with clindamycin (n = 50), sulfadiazine (n = 40), pyrimethamine (n = 33), trimethoprim-sulfamethoxazole (n = 16), and atovaquone (n = 10), alone or in combination. Twenty-two patients (40.0%) had a total of 27 ADRs. The most frequently occurring ADRs were rash (19 [34.5%]), mostly associated with sulfadiazine (9/40 [22.5%]) and clindamycin (6/50 [12.0%]), and gastrointestinal ADRs such as diarrhea (6 [10.9%]), stomach upset (6 [10.9%]), and bleeding (1 [1.8%]), mostly associated with clindamycin (5/50 [10.0%], 3/50 [6.0%], and 1/50 [2.0%], respectively). The incidence of ADRs associated with individual antitoxoplasmic drugs was 30.0% (3/10) for atovaquone, 26.0% (13/50) for clindamycin, 22.5% (9/40) for sulfadiazine, 12.5% (2/16) for trimethoprim-sulfamethoxazole, and 12.1% (4/33) for pyrimethamine. There were 2 serious ADRs: gastrointestinal bleeding in a patient treated with clindamycin and leukopenia in a patient treated with pyrimethamine. Twenty-five ADRs were reversed on drug discontinuation; the remaining 2 were mild and did not require drug discontinuation. CONCLUSIONS: The overall incidence of treatment-associated ADRs was high (40.0%) in these patients with ocular toxoplasmosis. The most frequently occurring ADRs were rash and gastrointestinal complaints.