T helper cell dysfunction in systemic lupus erythematosus (SLE): Relation to disease activity

Bermas, Bonnie L.; Petri, Michelle; Goldman, Daniel; Mittleman, Barbara; Miller, Matthew W.; Stocks, Naomi I.; Via, Charles S.; Shearer, Gene M.

doi:10.1007/bf01533366

Cited by 80 publications

(52 citation statements)

References 23 publications

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“…A diminished T helper cell response to influenza in patients with SLE, as measured by IL-2 secretion in the supernatant of the influenza-stimulated PBMCs of nonvaccinated patients, has been reported previously (10). We observed a decreased CD8ϩ T cell recall response to influenza antigens in patients with SLE, which is in accordance with results of a previous study (11).…”

Section: Discussionsupporting

confidence: 92%

“…Previous studies demonstrated a normal capacity of PBMCs from patients with SLE to respond to different stimuli, although diminished cellmediated responses may be present during active disease (10,(24)(25)(26). Because our cohort of patients with SLE had predominantly quiescent disease, this may explain their normal responses to SEB.…”

Section: Discussionmentioning

confidence: 76%

“…This decreased function could not be accounted for by the use of immunosuppressive agents alone and was shown to be associated with disease activity (10). In addition, lower levels of cell-mediated cytotoxicity against target cells infected with influenza A and influenza B have been observed in patients with SLE (11).…”

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confidence: 99%

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Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus

Holvast¹,

Assen²,

Haan³

et al. 2009

Arthritis & Rheumatism

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Objective. Both antibody and cell-mediated responses are involved in the defense against influenza. In patients with systemic lupus erythematosus (SLE), a decreased antibody response to subunit influenza vaccine has been demonstrated, but cell-mediated responses have not yet been assessed. This study was therefore undertaken to assess cell-mediated responses to influenza vaccination in patients with SLE.Methods. Fifty-four patients with SLE and 54 healthy control subjects received subunit influenza vaccine. Peripheral blood mononuclear cells and sera were obtained before and 1 month after vaccination. Cellmediated responses to A/H1N1 and A/H3N2 vaccines were evaluated using an interferon-␥ (IFN␥) enzymelinked immunospot assay and flow cytometry. Antibody responses were measured using a hemagglutination inhibition test.Results. Prior to vaccination, patients with SLE had fewer IFN␥ spot-forming cells against A/H1N1 compared with control subjects and a lower frequency of IFN␥-positive CD8؉ T cells. After vaccination, the number of IFN␥ spot-forming cells increased in both patients and control subjects, although the number remained lower in patients. In addition, the frequencies of CD4؉ T cells producing tumor necrosis factor and interleukin-2 were lower in patients after vaccination compared with healthy control subjects. As expected for a subunit vaccine, vaccination did not induce a CD8؉ T cell response. For A/H3N2-specific responses, results were comparable. Diminished cell-mediated responses to influenza vaccination were associated with the use of prednisone and/or azathioprine. The increase in A/H1N1-specific and A/H3N2-specific antibody titers after vaccination was lower in patients compared with control subjects.Conclusion. In addition to a decreased antibody response, cell-mediated responses to influenza vaccination are diminished in patients with SLE, which may reflect the effects of the concomitant use of immunosuppressive drugs. This may render these patients more susceptible to (complicated) influenza infections.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 76%

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Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus

Holvast¹,

Assen²,

Haan³

et al. 2009

Arthritis & Rheumatism

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“…In other systems, downregulation of responsiveness to recall antigens is associated with a decrease in T helper-1 type cytokines (10,17,21). In healthy pregnant women, PBMC have diminished IL-2 production after stimulation with recall antigens (11).…”

Section: Discussionmentioning

confidence: 99%

Proliferative responses to recall antigens are associated with pregnancy outcome in women with a history of recurrent spontaneous abortion.

Bermas

Hill

1997

J. Clin. Invest.

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Maternal tolerance of the fetal hemiallograft suggests that immunomodulation occurs during gestation. Therefore, recurrent spontaneous abortion (RSA) may represent a failure of the immune changes that maintain pregnancy. We hypothesized that fertile women but not women with RSA may lose their immune responses to recall antigens when pregnant. This phenomenon has been seen in immunosuppressed transplant recipients and is associated with graft survival. Therefore, we evaluated proliferative responses to recall antigens in four groups of women: group 1, nonpregnant fertile women with no history of pregnancy loss and at least one prior healthy pregnancy, n ϭ 13; group 2, nonpregnant women with a history of three or more spontaneous abortions, n ϭ 28; group 3, healthy pregnant women between 6 and 9 wk of gestation without a history of prior pregnancy loss, n ϭ 15; and group 4, pregnant women between 6 and 9 wk of gestation, with a history of RSA, n ϭ 22. Proliferative responses of peripheral blood leukocytes to the recall antigens influenza and tetanus, alloantigens, and phytohemagglutinin were determined prospectively. Positive responses (stimulation index Ͼ 3) to recall antigens (a response to either influenza or tetanus was considered positive) were as follows: group 1 (nonpregnant fertile women), 11/13 (85%); group 2 (nonpregnant RSA women), 24 / 28 (86%); group 3 (pregnant fertile women), 4/15 (27%) ( P Յ 0.007); and group 4 (pregnant RSA women), 13/22 (59%) ( P ϭ NS). In group 4, there was 100% fetal survival in the nine women who lost responsiveness to recall antigens; however, in the 13/22 patients who responded to recall antigens, 9/13 (69%) had a repeat spontaneous abortion. These findings suggest that immunosuppression, indirectly measured by proliferation to recall antigens, is necessary for early pregnancy maintenance. Furthermore, this approach may be useful for predicting pregnancy outcome for women with RSA and may provide a useful means for designing and monitoring therapies. ( J. Clin. Invest. 1997. 100:1330-1334.)

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“…Although the cause of this is unknown, it is thought that disease flares represent times of greatest immune dysfunction (35). To investigate whether changes in the level of immune dysfunction could affect the regulation of EBV infection, the frequency of virally infected cells was studied in patients with active and inactive disease.…”

Section: Sle Disease Activity Affects the Frequency Of Virally Infectmentioning

confidence: 99%

EBV and Systemic Lupus Erythematosus: A New Perspective

Gross

Hochberg²,

Rand

et al. 2005

The Journal of Immunology

201

178

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We have proposed that EBV uses mature B cell biology to access memory B cells as a site of persistent infection. A central feature of this model is that EBV adapts its gene expression profile to the state of the B cell it resides in and that the level of infection is stable over time. This led us to question whether changes in the behavior or regulation of mature B cells would alter the state of EBV persistence. To investigate this, we studied the impact of systemic lupus erythematosus (SLE), a disease characterized by immune dysfunction, on EBV infection. We show that patients with SLE have abnormally high frequencies of EBV-infected cells in their blood, and this is associated with the occurrence of SLE disease flares. Although patients with SLE have frequencies of infected cells comparable to those seen in immunosuppressed patients, in SLE the effect was independent of immunosuppressive therapy. Aberrant expression of viral lytic (BZLF1) and latency (latency membrane proteins 1 and 2a) genes was also detected in the blood of SLE patients. We conclude that the abnormal regulation of EBV infection in SLE patients reflects the sensitivity of the virus to perturbation of the immune system.

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T helper cell dysfunction in systemic lupus erythematosus (SLE): Relation to disease activity

Cited by 80 publications

References 23 publications

Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus

Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus

Proliferative responses to recall antigens are associated with pregnancy outcome in women with a history of recurrent spontaneous abortion.

EBV and Systemic Lupus Erythematosus: A New Perspective

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