Background/Purpose: Reactivation of chronic herpesvirus infections is not uncommon in immunosuppressed patients, including those with granulomatosis with polyangiitis (GPA).  The effects of GPA disease and therapy on cell-mediated immunity against herpesviruses are not well established.   Although immunosuppressive therapy is clearly associated with viral reactivation disease, data from other cohorts demonstrate that altered immunocompetence from other infections may also be an important contributing factor. We examined the effects of recent and acute infections on cell-mediated immune response against influenza and herpesvirus antigens in a well-characterized cohort of patients with GPA.

Methods: Twenty GPA patients (mean age: 56 years; 55% female; 100% Caucasian) and 5 age-, race-, and gender-matched healthy controls were prospectively enrolled. Disease features, medications, current and recent infection data, and disease activity scores were obtained. Extended ELISPOTs for interferon-gamma (IFNg) production to CEF and VZV antigens were assessed.

Results: GPA patients had a median disease duration of 86.8 (54) months, median BVAS of 1.0 and VDI of 2.0. Prednisone was used in 15 (75%) of the patients (median dose: 12.5 mg) and steroid-sparing immunosuppressive agents in 14 (70) %; two patients were not receiving IS therapy. An active infection was identified in 30% of the patients at study entry, and 50% had a recent serious infection within the past year.  GPA patients had a significant decline in IFNg median responses to CEF & VZV antigens with increasing prednisone dose (0mg=450 & 192.1; <11mg= 161.8, 7.3; 11-60mg= 202.5, 24.2; 1000mg= 22.5, 25.5) (p=0.21, 0.041 respectively) and with the number of immunosuppressive agents used ( none= 457, 192.5; one= 161.3, 129.3;  two or more= 202.5, 18.5) (none vs. one=0.53, 0.8; none vs. two: p=0.095, 0.095 ).  The presence of an active infection at study entry was associated with a decrease in VZV IFNg response (p=0.024). However, prior herpesvirus infection (1 HSV pneumonia, 4 VZV disease) within the past year was associated with higher CEF response (p=0.036) and a trend towards higher VZV responses (p=0.099).

Conclusion: Immunosuppressive therapy and non-viral infections both decrease cell-mediated immune response against herpes viruses, potentially leading to reactivation disease in patients with GPA, as seen in other immunosuppressed populations. Prior herpesvirus infection is associated with increases in both CEF and VZV responses, suggesting a possible “crossover” protective effect against both CMV and VZV reactivation, which could be important when considering the need and timing of prophylactic interventions.  .

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cell-mediated-immune-responses-to-influenza-and-herpesvirus-antigen-stimulation-are-conserved-but-adversely-impacted-by-immunosuppressive-therapy-and-active-infection-in-patients-with-granulomatosis-w/