Differences in regulatory T cells between Churg-Strauss syndrome and chronic eosinophilic pneumonia with asthma

doi:10.1016/j.jaci.2008.05.040

Journal of Allergy and Clinical Immunology

Volume 122, Issue 3, September 2008, Pages 610-616

https://doi.org/10.1016/j.jaci.2008.05.040 Get rights and content

Background

Chronic eosinophilic pneumonia (CEP) with asthma precedes the onset of Churg-Strauss syndrome (CSS) in half of all patients with CSS. It is not known what determines whether patients with CEP after asthma will have CSS.

Objective

We examined whether activation of regulatory T cells in patients with CEP inhibits CSS development and is otherwise involved in the mechanism of CSS disease.

Methods

In patients with CSS (n = 38), CEP with asthma (n = 20), and general adult asthma (n = 108), we examined the number of CD4⁺CD25⁺ T cells in peripheral blood, as well as levels of expression of the cytokines IL-2, IL-5, IL-10, and TGF-β by CD4⁺CD25⁺ T cells, CD4⁺CD25⁻ T cells, or both.

Results

At disease onset, patients with CSS, unlike patients with CEP, had significantly fewer CD4⁺CD25⁺ T cells than patients with any step of asthma. CD4⁺CD25⁺ T cells producing IL-10 were rarely detected in patients with CSS at disease onset or relapse, whereas the numbers of IL-10–producing T cells in patients with CEP were high at disease onset. There were fewer CD4⁺CD25⁻ T cells producing IL-2 in patients with CSS before treatment than in patients with CEP at disease onset. The proportions of CD4⁺CD25⁺ T cells producing IL-10 and CD4⁺CD25⁻ T cells producing IL-2 in patients with CSS increased at remission.

Conclusions

Maintenance of the numbers of regulatory T cells in patients with CEP with asthma might inhibit CSS development through the action of cytokines, such as IL-10 and IL-2, produced by CD4⁺CD25⁺ or CD4⁺CD25⁻ T cells. This might be part of a mechanism that influences progression and prognosis in these diseases.

Section snippets

Patients

We recruited 38 patients with CSS, 20 patients with CEP with asthma, and 108 adult patients with general asthma (non-CSS and non-CEP) treated between January 2003 and May 2007 at the Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara, Kanagawa, Japan. All 108 adult patients with general asthma were given diagnoses according to the criteria of the Global Initiative for Asthma (GINA) guidelines,³⁶ and the severity of their asthma was classified as

Clinical findings

There were more women than men with CSS and CEP, but there was no significant difference in the sex ratio among patients with asthma at any step. Thirty-eight patients with CSS and 15 of the 20 patients with CEP had been classified according to the GINA guidelines as having severe asthma at the first hospital visit (Table I). There was no significant difference in the age of onset of asthma between those who had CSS or CEP. Patients with CEP and asthma did not go on to have CSS during the

Discussion

CSS is a rare vasculitis with an annual incidence of approximately 2.4 to 6.8 cases per 1 million persons.40, 41 The report by Guillevin et al² revealed some triggering factors that preceded the onset of the disease by up to several months, including desensitization, rapid discontinuation of oral corticosteroids, and vaccination. The cause and pathogenesis, and especially the heritability, of CSS are still unknown. In a rare case of familial CSS in 2 sisters, it was not possible to explain the

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: Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

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Mechanisms of allergy and clinical immunologyDifferences in regulatory T cells between Churg-Strauss syndrome and chronic eosinophilic pneumonia with asthma

Background

Objective

Methods

Results

Conclusions

Section snippets

Patients

Clinical findings

Discussion

Rheum Dis Clin North Am

Mod Pathol

J Allergy Clin Immunol

Cell

J Autoimmun

J Neuroimmunol

Cytotherapy

Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Clin Immunol Immunopathol

Semin Arthritis Rheum

Chest

Ann Allerg Asthma Immunol

Allergic granulomatosis, allergic angiitis, and periarteritis nodosa

Am J Pathol

Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients

Medicine

Allergic granulomatosis and angiitis (Churg-Strauss syndrome)

Mayo Clin Proc

Chronic eosinophilic pneumonia (CEP) as a presenting feature of Churg-Strauss syndrome (CSS)

Eur Respir J

Idiopathic chronic eosinophilic pneumonia

Semin Respir Crit Care Med

Eosinophilic pneumonias

Allergy

A specific elevation of RANTES in bronchoalveolar lavage fluids of patients with chronic eosinophilic pneumonia

Lab Invest

Elevated levels of thymus- and activation- regulated chemokine in bronchoalveolar lavage fluid from patients with eosinophilic pneumonia

Am J Respir Crit Care Med

Elevated interleukin-18 levels in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia

Allergy

Activated and memory alveolar T-lymphocytes in idiopathic eosinophilic pneumonia

Eur Respir J

Mechanisms of allergy and clinical immunology
Differences in regulatory T cells between Churg-Strauss syndrome and chronic eosinophilic pneumonia with asthma