Abstract

Background: High levels of IL4 secretion and IgE synthesis characterize allergic respiratory diseases. Individuals infected with HTLV-I virus have spontaneous T-cell proliferation and high levels of IFN gamma production, which are immunological functions associated with a Th1 type of immune response. Objective: To relate the occurrence of HTLV-I infection in an atopic patient with symptomatic asthma. Methods: In this case report, the authors relate the presence of two supposedly antagonic immune diseases in the same patient. Results: The patient is a 45-year-old white woman with a history of asthma and allergic rhinitis in the last 10 years. Asthmatic symptoms were present and were triggered after exposure to dust and mold. Her HTLV-I seropositive status was detected by chance five years ago during a routine screening for blood donation. White blood counts revealed 7,800 leucocytes and 156 eosinophils (2%). Skin prick tests were positive for D. pteronyssinus (4 mm), D. farinae (3 mm) and Blomia tropicalis (4 mm). Negative control with saline did not elicit any skin reaction. Histamine positive control led to a 5 mm wheal. Cytokine levels in the PBMC supernatant were: IFNϒ = 1195 pg/dl, TNF∝ = 460 pg/dl, IL10 = 265 pg/dl, IL5 = 41 pg/dl. Conclusion: In spite of a predominant Th1 response (very high IFNϒ levels) and low levels of IL-5, asthmatic symptoms continued to be observed in this patient.

Introduction

The functional classification of murine CD4⁺ T-helper cell clones into distinct subtypes, nominated Th1 and Th2, based primarily on the pattern of their cytokine production, has enhanced our understanding of T-cell biology (1). Th1 cells are characterized by the production of IL-2, IFNϒ and TNF-β , whereas Th2 cells produce IL-4, IL-5, IL-6 and IL-13 (1,2). Previous studies have shown that Th1/Th2 cells play different roles in infectious and allergic diseases (3,4,5,6).

With respect to human retroviruses, it has been observed that individuals infected with HTLV-I virus have spontaneous T-cell proliferation and high levels of IFN production, which are immunological functions associated with a Th1 type of immune response (6,7,8,9,10,11). Allergic diseases, on the other hand, are associated with higher levels of IL-4, IL-5 and IL-13, which promote IgE production. Distinct patterns of immune regulation in different illnesses, particularly in allergic and autoimmune diseases, have been observed and implicated in the immune deviation toward the strongest stimulus (11,12,13). Previous studies in patients infected with HTLV-I and Strongyloides stercoralis have shown that this virus induces high levels of IFN production and a suppression of Th2 cytokines (4,5). Based on this information, milder or no clinical manifestation of allergic asthma would be expected in HTLV-I infected subjects.

In this case study, the authors report on the presence of two supposedly antagonic immune diseases in the same patient, a 45-year-old white female with allergic asthma and rhinitis, infected with the HTLV-I virus.

Objective

The aim of this case study was to report the occurrence of HTLV-I infection in an atopic subject, resulting in high IFN gamma production but no changes in the course of asthma.

Case report

The subject is a 45-year-old white woman with a history of asthma and allergic rhinitis over the past 10 years. Asthmatic symptoms such as dyspnea, coughing and wheezing were present and were triggered after exposure to domestic dust and mold. Nocturnal asthmatic symptoms were observed once a week. Nasal itching and lacrimation were associated with the asthmatic complaints. The patient had experienced atopic symptoms with no remission periods since childhood and she required treatment with an inhaled steroid (budesonide; 800 mcg daily) and a long-term β2 agonist (formoterol, 12mcg bid).

Her HTLV-I seropositivity was detected by chance five years ago during a routine screening for blood donation and was confirmed by ELISA and Western-blot assays. The patient reported having received a blood transfusion ten years ago.

Physical examination revealed that the patient was apparently in good health. Her blood pressure was normal. Her nasal passages were moderately blocked by turbinate hypertrophy and swelling of the mucosa, which was congested and humid. Lung auscultation revealed a bilateral reduced murmur and wheezing. No arrhythmias or any other heart disturbances were detected on chest examination. No abnormalities were found in the extremities. A complete neurological exam searching for mild manifestations of HTLV-I-related myelopathy revealed no abnormalities.

Spirometry (14) showed a moderate obstruction with a significant response after use of a bronchodilator (salbutamol 400 mcg) - FEV₁ = 45% and 64% of the predicted values, respectively. Chest radiography was normal. White blood counts revealed 7,800 leukocytes and 2% eosinophils. Skin prick tests (15) were positive for Dermatophagoides pteronyssinus (4 mm), Dermatophagoides farinae and Blomia tropicalis (3 mm). Negative control with saline did not elicit any skin reaction. Histamine positive control led to a 5 mm flare.

Serum total IgE was 147 KUI/L (MEIA) and specific IgE to Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis were 1,520 KU/L, 2,100 KU/L and 2,100 KU/L, respectively. Cytokine levels in the PBMC supernatant were: IFNϒ = 1195 pg/dl, TNF∝ = 460 pg/dl, IL10 = 265 pg/dl, IL5 = 41 pg/dl.

Discussion

Atopy is the single strongest risk factor for the development of asthma. From an immunological standpoint, allergic diseases are characterized by a Th2 cytokine profile, increased IL-4 and IL-5, and activation of mast cells and basophils.

There is evidence that high IFN gamma production suppresses the allergic immune response and may protect against asthma (2,4,5,6,7,8). Shirakawa and colleagues evaluated the effect of repeated Th1 stimuli through BCG vaccination (at 5 and 12 years of age) on cytokine profiles in atopic Japanese schoolchildren. They observed an inverse correlation between tuberculin reactions and atopy (16).

The human T lymphotropic virus, type I, is a retrovirus linked to hematological and neurological disorders. It has T-cell tropism (CD4⁺ and CD8⁺), which causes T-cell proliferation and establishes persistent infection (9). It also stimulates the production of high levels of IFNϒ MIP-1 , -1 and IL-16 (7,8). The increased levels of IFNϒ produced by HTLV-I - infected T-cells may down-regulate a Th2 immune response. Porto et al have observed an inverse correlation between IFNϒ , IgE and IL-5 and a direct relationship between IFNϒ response and IL-10 in HTLV-I seropositive patients co-infected with Strongyloides stercoralis (4). The HTLV-I infection decreases the sensitivity of S. stercoralis-specific IgE, the size of the immediate hypersensitivity skin reaction and the sensitivity of these tests in the diagnosis of strongyloidiasis (5). IgE and IL-5 suppression was not observed in the present case although a moderate decrease in IL-10 level was observed.

Th1 and Th2 responses have often been viewed as being mutually exclusive. However, it has recently been shown that Th1 and Th2 may coexist in the lung and can cooperate to generate eosinophilic inflammation. Furthermore, Th1 cells may induce alterations in the lung microenvironment such as secretion of chemokines and adhesion molecules expression that may potentiate Th2 cell recruitment to the airways (17).

In this case report, despite the strong Th1 immune response with increased IFNϒ production (in PBMC non-stimulated culture supernatant), no suppression of the Th2 response or of the clinical manifestations of asthma was observed.

Conclusions

The high IFNϒ production observed in this asthmatic subject, found to be HTLV-I seropositive after a blood transfusion ten years before, did not interfere with her atopy markers, such as specific IgE or SPT reactivity, nor in the intensity of her asthma manifestation or her level of IL-5. It seems that in special situations Th1 and Th2 cytokine profiles may coexist in the same patient. This co-existence suggests that atopy and its immune regulation is not an all-or-nothing condition but that a spectrum of situations may exist, ranging from non-atopic with normal T-cell IFNϒ production to highly atopic with high impairment of T-cell IFNϒ production. In addition, many distinct factors such as genetic background, the environment, route and timing of exposure to antigens and infections may regulate the expression of atopic disorders.

Correspondence to

Adelmir de Souza-Machado, MD. Rua Osvaldo Valente 602/1102, ITAIGARA CEP: 41.815-090 Salvador BA, Brazil. e-mail: adelmirm@atarde.com.br Phone: + (5571) 339 6285 Fax: + (5571) 452 0494

References