Delayed Hypersensitivity Skin Test Research Articles

Influence of Honey on Immune Status in Mice-Bearing Ehrlich Carcinoma

Honey is currently the focus of many research projects due to its varied biological activities including antiinflammatory, antioxidant, antibacterial, antihypertensive and hypoglycemic effects. In the current study antitumor effect of coriander honey was investigated in mature mice bearing Ehrlich ascites carcinoma (EAC) with special reference to immune status. Coriander honey (500 mg/kg) caused decrease in tumor volume, packed cell volume and viable cell count, and caused increase in non-viable cell count and mean survival time thereby increasing life span of EAC bearing mice. The study of the effect of honey on immunological status in mice bearing Ehrlich carcinoma showed that the levels of immunoglobulin M, G and A were increased following the administration of coriander honey. It was also clear that coriander honey increased the phagocytic activity in mice bearing Ehrlich carcinoma. There was reduction in the stimulation indices of lymphocyte transformation of mice bearing Ehrlich carcinoma. Delayed hypersensitivity skin test revealed that the Ehrlich carcinoma reduced the reaction after 72 hours post inoculation with bovine serum albumin. The administration of honey caused the rise in skin thickness as shown in Ehrlich carcinoma and subsequently treated with coriander honey with a rise of 0.61 mm as compared with 0.52 mm in EAC control group. The skin thickness in coriander honey group was the highest among all groups with 0.90 mm thickness. Based on these results, it can be concluded that coriander honey exhibited antitumor effect by modulating cell mediated immune response and immunoglobulin levels, in EAC bearing mice.

Clinical value of radiocontrast media skin tests as a prescreening and diagnostic tool in hypersensitivity reactions

BackgroundSome radiocontrast media (RCM) hypersensitivity reactions may have underlying IgE- or T-cell–mediated mechanisms. RCM skin testing may be useful for predicting future reactions. ObjectiveTo investigate the clinical value of RCM skin testing before computed tomography and after RCM hypersensitivity reactions. MethodsPatients who underwent RCM skin testing were a prospective sample of convenience at a single medical center and were tested just before their pending nonionic RCM-enhanced computed tomogram. In addition, skin test data of patients who were referred to the allergy clinic because of their previous RCM hypersensitivity reactions were reviewed retrospectively. ResultsA total of 1048 patients enrolled in the study prospectively. Of these, 672 (64.1%) had never been exposed to RCM. Of the 376 previously exposed to RCM, 61 (16.2%) had a history of at least one mild RCM-associated reaction, 56 (91.8%) had immediate reactions, and 5 had no-immediate reactions. There was only 1 positive immediate hypersensitivity RCM skin test result (0.09%). There were 51 mild immediate reactions (4.9%), 1 moderate immediate reaction (0.09%), 8 mild nonimmediate reactions (0.76%), and 1 moderate nonimmediate reaction (0.09%). There was only 1 positive delayed hypersensitivity skin test result (0.09%), retrospectively determined, in 1 (11.1%) of the nonimmediate RCM-associated reactions. Sensitivity of RCM skin testing was significantly higher with severe immediate reactions (57.1%) than mild reactions (12.9%) and moderate reactions (25.0%) in the retrospective review of diagnostic skin test data (P = .03). ConclusionRCM skin testing for screening is of no clinical utility in predicting hypersensitivity reactions. RCM skin testing may have modest utility in retrospectively evaluating severe adverse reactions.

Polyphasic Taxonomic Analysis Establishes Mycobacterium indicus pranii as a Distinct Species

Background Mycobacterium indicus pranii (MIP), popularly known as Mw, is a cultivable, non-pathogenic organism, which, based on its growth and metabolic properties, is classified in Runyon Group IV along with M. fortuitum, M. smegmatis and M. vaccae. The novelty of this bacterium was accredited to its immunological ability to undergo antigen driven blast transformation of leukocytes and delayed hypersensitivity skin test in leprosy patients, a disease endemic in the Indian sub-continent. Consequently, MIP has been extensively evaluated for its biochemical and immunological properties leading to its usage as an immunomodulator in leprosy and tuberculosis patients. However, owing to advances in sequencing and culture techniques, the citing of new strains with almost 100% similarity in the sequences of marker genes like 16S rRNA, has compromised the identity of MIP as a novel species. Hence, to define its precise taxonomic position, we have carried out polyphasic taxonomic studies on MIP that integrate its phenotypic, chemotaxonomic and molecular phylogenetic attributes.Methodology/Principal FindingsThe comparative analysis of 16S rRNA sequence of MIP by using BLAST algorithm at NCBI (nr database) revealed a similarity of ≥99% with M. intracellulare, M. arosiense, M. chimaera, M. seoulense, M. avium subsp. hominissuis, M. avium subsp. paratuberculosis and M. bohemicum. Further analysis with other widely used markers like rpoB and hsp65 could resolve the phylogenetic relationship between MIP and other closely related mycobacteria apart from M. intracellulare and M. chimaera, which shares ≥99% similarity with corresponding MIP orthologues. Molecular phylogenetic analysis, based on the concatenation of candidate orthologues of 16S rRNA, hsp65 and rpoB, also substantiated its distinctiveness from all the related organisms used in the analysis excluding M. intracellulare and M. chimaera with which it exhibited a close proximity. This necessitated further analysis of MIP with more sensitive and segregating parameters to ascertain its precise taxonomic position as a new species. The analysis of MIP and its comparison with other mycobacterial reference strains based on cellular and biochemical features, growth characteristics and chemotaxonomic studies like FAME profiling confirmed that MIP is uniquely endowed with diverse metabolic attributes that effectively distinguishes it from all the closely related mycobacteria including M. intracellulare and M. chimaera.ConclusionThe results presented in this study coupled with the non-pathogenic nature and different biochemical and immunomodulatory properties of MIP affirm it as a distinct species belonging to M. avium complex (MAC). It is further proposed to use an earlier suggested name Mycobacterium indicus pranii for this newly established mycobacterial species. This study also exemplifies the growing need for a uniform, consensus based broader polyphasic frame work for the purpose of taxonomy and speciation, particularly in the genus Mycobacterium.

Use of granulocyte-macrophage colony-stimulating factor to reverse anergy in otherwise immunologically healthy children

T-cell anergy, as measured by delayed hypersensitivity skin testing, is associated with increased susceptibility to infection. Because the repertoire of effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) includes enhancement of antigen processing and presentation by antigen-presenting cells, GM-CSF has been used to augment immune function in human immunodeficiency virus-induced and other viral illness-induced immune dysfunction and to affect positively immune function in a wide variety of disorders. To attempt reversal of T-cell anergy using GM-CSF in 3 otherwise immunologically healthy children with severe recurrent and persistent viral respiratory tract infections and in one child with recurrent bacterial sepsis. After written informed consent and baseline data were obtained, the study participants were administered 3 two-week cycles of GM-CSF. Delayed hypersensitivity skin testing and laboratory tests were repeated 2 weeks after the third cycle and subsequently as clinically indicated. All 4 children developed delayed hypersensitivity by skin testing, and all demonstrated markedly decreased number and severity of infection. Improvement persisted in all patients for at least 1 year. A single cycle of additional treatment in 2 patients reestablished delayed hypersensitivity and decreased infection, both of which persisted throughout the follow-up period of 4 or more years. GM-CSF treatment reversed T-cell anergy in 4 children. Reestablishment of delayed hypersensitivity was associated with a significant decrease in infection. Although further studies will be needed, use of GM-CSF should be considered as an immune modulator in patients with T-cell anergy and recurrent infections.

Evidence for Antigen-Specific Immune Deviation in Patients With Acute Retinal Necrosis

Background: Because experimental acute retinal necrosis (ARN) induced by herpes simplex virus in mice develops only if mice fail to acquire virus-specific delayed hypersensitivity (DH), although they produce antiviral antibodies (ie, anterior chamber–associated immune deviation), we sought to determine whether a similar inverse correlation exists for patients with varicellazoster virus (VZV)-induced ARN. Design: Patients with acute, VZV-induced ARN and agematched control subjects were skin tested with VZV and purified protein derivative antigens to evaluate DH. Varicella-zoster virus–induced ARN was diagnosed using polymerase chain reaction and intraocular antibody quotient. Serum samples were collected and analyzed for anti-VZV and anti–herpes simplex virus antibody titers. Acute retinal necrosis activity was assessed clinically, and DH skin tests were repeated 3 months after onset when ocular recovery had taken place. Result: Whereas controls displayed intense DH when tested with VZV and purified protein derivative antigens, a subset of patients with ARN displayed absent VZV-specific DH (although their purified protein derivative responses were normal). Patients with the most severe ARN had the lowest DH responses to VZV antigens. Serum anti-VZV antibody titers were higher in patients with ARN than in controls, and antiviral titer correlated inversely with the intensity of anti-VZV DH responses. Varicella-zoster virus–specific DH responses were restored in patients who recovered from ARN. Conclusion: Varicella-zoster virus-ARN develops in a setting where DH reactivity to viral antigens is absent, implying that virus-specific DH might ameliorate the severity of ARN. Clinical Relevance: Linking virus-specific DH to vulnerability to ARN in individuals infected with VZV might reveal an underappreciated pathogenic mechanism.

Value of nutritional parameters in the prediction of postoperative complications in elective gastrointestinal surgery.

The following nutritional parameters were assessed in 117 patients before major gastrointestinal surgery: percentage recent weight loss: percentage ideal body weight; tricipital skinfold; arm muscular area; grip strength dynamometry; serum albumin (ALB); serum transferrin (TFN); delayed hypersensitivity skin tests (DH); total lymphocyte count; prognostic nutritional index (PNI) and clinical assessment of malnutrition. Comparing the results in patients without complications (n = 99) with those in patients with complications (n = 18) and the results in patients who survived (n = 109) with those who died (n = 8), we found that only ALB, DH, TFN and PNI showed significant differences in both comparisons. Correlations of complications with combined parameters was made by multiple linear regression analysis; a modified PNI (mPNI), including these three single variables, has emerged. Considering its risk values, the nutritional parameters showed the following sensitivity and specificity, respectively: ALB less than 3.2 g/dl (72 and 71 per cent), anergy (67 and 64 per cent), TFN less than 205 mg/dl (67 and 55 per cent) and mPNI less than 20 (72 and 70 per cent). Using Bayes' theorems, ALB, DH and calculated indices showed the same predictive capacity and we conclude that single or multiple association of nutritional parameters have no additive effect. To predict complications of nutritional origin it seems only necessary to consider ALB, taking into account the type of operation and the normal duration of postoperative hospital stay without oral intake.

Further observations on clinical, histopathological, and immunological features of borderline disseminated cutaneous leishmaniasis caused by Leishmania (Leishmania) amazonensis

Leishmania (Leishmania) amazonensis has for some time been considered as the causative agent of two distinct forms of American cutaneous leishmaniasis (ACL): localized cutaneous leishmaniasis (LCL), and anergic diffuse cutaneous leishmaniasis (ADCL). Recently, a new intermediate form of disease, borderline disseminated cutaneous leishmaniasis (BDCL), was introduced into the clinical spectrum of ACL caused by this parasite, and in this paper we record the clinical, histopathological, and immunological features of eight more BDCL patients from Brazilian Amazonia, who acquired the disease in the Pará state, North Brazil. Seven of them had infections of one to two years' evolution and presented with primary skin lesions and the occurrence of metastases at periods varying from six to 12 months following appearance of the first lesion. Primary skin lesions ranged from 1-3 in number, and all had the aspect of an erythematous, infiltrated plaque, variously located on the head, arms or legs. There was lymphatic dissemination of infection, with lymph node enlargement in seven of the cases, and the delayed hypersensitivity skin-test (DTH) was negative in all eight patients prior to their treatment. After that, there was a conversion of DTH to positive in five cases re-examined. The major histopathological feature was a dermal mononuclear infiltration, with a predominance of heavily parasitized and vacuolated macrophages, together with lymphocytes and plasma cells. In one case, with similar histopathology, the patient had acquired his infection seven years previously and he presented with the largest number of disseminated cutaneous lesions. BDCL shows clinical and histopathological features which are different from those of both LCL and ADCL, and there is a good prognosis of cure which is generally not so in the case of frank ADCL.

Damage Control Orthopaedics

In some groups of polytrauma patients, particularly those with chest injuries, head injuries, and those with mangled extremities, early total care of major bone fractures may be potentially harmful. Delaying all orthopaedic surgery, however, is also not always the best approach. In these situations, damage control orthopaedics, which emphasizes the stabilization and control of the injury rather than repair will add little additional physiologic insult to the patient and is a treatment option that should be considered.

A phase I study of immunotherapy with tumor cell-dendritic cell fusion vaccine in patients with advanced or recurrent gastrointestinal cancer

2615 Background: Immunotherapy with tumor cell-dendritic cell fusion vaccine has been shown to induce the immune response against multiple tumor antigens including unknown tumor antigens. The aim of this study was to test safety, feasibility, and clinical response of immunotherapy with tumor cell-dendritic cell fusion vaccine. Methods: Nine patients with advanced or recurrent gastrointestinal cancer that is unresponsive to standard surgical therapy and chemotherapy were enrolled in this study after informed consent was obtained. Monocytes were separated from the peripheral blood by leukapheresis and were cultured with GM-CSF and IL-4 for 6 days. Then TNFα, IL-1β, IL-6, and PGE2 were added for maturation of dendritic cells. Fusion of irradiated tumor cells and dendritic cells was created by polyethylene glycol and electroporation. Fusion vaccine was subcutaneously injected in the inguinal region four times every two weeks. Safety and adverse effects were evaluated after vaccination. Delayed hypersensitivity skin-test, cytokine array, Th1/Th2, Tc1/Tc2, and clinical response were compared before and after vaccination. Results: There were neither adverse effects nor autoimmune responses after vaccination in all the patients. Delayed skin tests became positive in six of nine patients after vaccination. Th1/Th2 balance and Tc1/Tc2 balance were improved in six of nine patients after vaccination. IAP levels were decreased in five patients after vaccination. Clinical response was stable disease in five patients and progressive disease in four patients. Conclusions: Safety and feasibility of immunotherapy with tumor cell-dendritic cell fusion vaccine were confirmed in patients with advanced or recurrent gastrointestinal cancer by this study. No significant financial relationships to disclose.

A phase I study of immunotherapy with tumor cell-dendritic cell fusion vaccine in patients with advanced or recurrent gastrointestinal cancer

2615 Background: Immunotherapy with tumor cell-dendritic cell fusion vaccine has been shown to induce the immune response against multiple tumor antigens including unknown tumor antigens. The aim of this study was to test safety, feasibility, and clinical response of immunotherapy with tumor cell-dendritic cell fusion vaccine. Methods: Nine patients with advanced or recurrent gastrointestinal cancer that is unresponsive to standard surgical therapy and chemotherapy were enrolled in this study after informed consent was obtained. Monocytes were separated from the peripheral blood by leukapheresis and were cultured with GM-CSF and IL-4 for 6 days. Then TNFα, IL-1β, IL-6, and PGE2 were added for maturation of dendritic cells. Fusion of irradiated tumor cells and dendritic cells was created by polyethylene glycol and electroporation. Fusion vaccine was subcutaneously injected in the inguinal region four times every two weeks. Safety and adverse effects were evaluated after vaccination. Delayed hypersensitivity skin-test, cytokine array, Th1/Th2, Tc1/Tc2, and clinical response were compared before and after vaccination. Results: There were neither adverse effects nor autoimmune responses after vaccination in all the patients. Delayed skin tests became positive in six of nine patients after vaccination. Th1/Th2 balance and Tc1/Tc2 balance were improved in six of nine patients after vaccination. IAP levels were decreased in five patients after vaccination. Clinical response was stable disease in five patients and progressive disease in four patients. Conclusions: Safety and feasibility of immunotherapy with tumor cell-dendritic cell fusion vaccine were confirmed in patients with advanced or recurrent gastrointestinal cancer by this study. No significant financial relationships to disclose.

Effects of zinc on cell-mediated immunity in chronic hemodialysis patients.

Thirteen healthy subjects and 20 hemodialysis patients were studied to observe the delayed hypersensitivity skin tests (DHSTs) and phytohemagglutinin (PHA)-stimulating lymphocyte blastogenesis. Significant differences were observed between the groups. Controls had a higher proportion of positive skin reaction than hemodialysis patients in relation to Escherichia coli (p<0.01) and tuberculin (PPD) (p<0.05). Regarding lymphocyte blastogenesis stimulated by phytohemagglutinin (PHA), cell proliferation was more accentuated in controls than hemodialysis patients (p<0.05). On the other hand, serum zinc was elevated in controls (78 +/- 8 microg/dL) in comparison to hemodialysis patients (71 +/- 33 microg/dL) (p<0.05). Of the 20 hemodialysis patients, 8 patients were maintained on long-term hemodialysis before and after zinc therapy, with the aim of studying DHST and PHA-stimulating lymphocyte blastogenesis. There was a significant improvement of DHST response to E. coli antigen after 100 d of zinc treatment (p<0.01), and with the discontinuation of therapy, the DHST responses decreased back to the initial values (p<0.05). Zinc administration also increased the lymphocyte proliferation induced by PHA from 31386 +/- 3974 to 42480 +/- 5242 cpm (mean +/- SD) (p<0.05). These results indicated that zinc therapy improved in vivo and in vitro DHST and lymphocyte function of hemodialysis patients and that its discontinuation suppressed all of the benefits observed.

Immune deviation and ocular infections with varicella zoster virus

Since experimental, herpes simplex virus-induced acute retinal necrosis (ARN) develops in mice only if the mice fail to acquire virus-specific delayed hypersensitivity (DH) and despite their production of anti-viral antibodies (i.e. ACAID), I investigated whether a similar situation exists for patients with either varicella zoster virus (VZV)-induced ARN or anterior uveitis caused by VZV. Patients with either acute VZV-induced ARN, anterior uveitis with dermatitis (herpes zoster ophthalmicus, ZO-AU), or anterior uveitis without dermatitis (zoster sine herpete, ZSH-AU) were skin-tested with VZV to evaluate DH. The formal diagnoses of ARN associated with VZV, ZO-AU, and ZSH-AU were established by PCR analysis of the ocular samples and/or by the Goldmann-Witmer coefficient to determine levels of local antibody production. ARN, ZO-AU, and ZSH-AU activity were assessed clinically, and DH skin tests were repeated three months after onset when ocular recovery had taken place. All patients with VZV-induced skin disease alone (control group) displayed intense DH when tested with VZV antigen. In contrast, subsets of patients with ARN or ZO-AU displayed loss of VZV-specific DH. Patients with the most severe ARN or ZO-AU had the lowest DH responses to VZV antigens. Serum anti-VZV antibody titers were higher in ARN patients than in normal controls, and the anti-viral titer correlated inversely with the intensity of anti-VZV DH responses. VZV-specific DH responses were restored in patients who recovered from ARN. Patients with ZSH-AU also failed to display VZV-specific DH. The absence of DH reactivity to VZV antigens (i.e. immune deviation) appears to be a concomitant feature of VZV uveitis of high intensity, implying that virus-specific DH may interfere with the emergence of VZV-induced ARN or anterior uveitis.

High-Dose Inhaled Fluticasone and Delayed Hypersensitivity Skin Testing

Systemic steroids have been associated with anergy. Treatment with high-dose inhaled steroids has many documented systemic side effects, including adrenal suppression, reduction in growth velocity, and increased bone metabolism; however, little is known about their effect on delayed-type hypersensitivity (DTH). The purpose of this study was to determine if a 28-day course of high-dose inhaled fluticasone suppresses DTH to a standard panel of antigens. Forty-five healthy, steroid-naïve subjects volunteered for this randomized, double-blinded, placebo-controlled trial. All subjects had baseline DTH assessed by intradermal skin testing to a standard panel of antigens (tetanus, candida, mumps, and tuberculin) read 72 h after placement. Subjects were then randomized to receive placebo or high-dose inhaled fluticasone (880 micro g/d) for 28 days, after which a second DTH panel was performed. A third DTH panel was performed after a 30-day washout period. Of the 45 enrolled subjects, 38 subjects completed the study, including 20 subjects in the placebo group and 18 subjects in the drug group. There was no significant difference in the amount of induration between drug and placebo groups for any of the three periods tested. Twenty-eight days of treatment with high-dose inhaled fluticasone did not suppress DTH in healthy volunteers.

Body composition changes in cachectic patients receiving home parenteral nutrition.

The purpose of this study was to evaluate the initial body compositional changes experienced by malnourished patients requiring home parenteral nutrition (HPN) for repletion. Eight patients were prospectively studied for 3 months. Body composition was determined by dual-energy X-ray absorptiometry (DXA), and a comprehensive nutrition assessment was performed including body weight, visceral proteins, triceps skinfold (TSF), midupper arm circumference (MUAC), midupper arm muscle circumference (MUAMC), body mass index (BMI), delayed hypersensitivity skin tests (DHST), and diet history. Body composition measured by DXA showed an increase in (mean +/- SD) total fat from 5770 +/- 2805 to 10581 +/- 1980 g (p < .001) and bone mineral content from 2155 +/- 429 to 2190 +/- 443 g (p = .047). Lean soft tissue remained unchanged. Body weight and BMI increased from 47.7 +/- 6.6 to 53.6 +/- 8.2 kg (p = .006) and from 16.6 +/- 1.5 to 18.6 +/- 1.5 kg/m2 (p = .005), respectively. TSF increased from 6.3 +/- 3.1 to 10.4 +/- 4.0 mm (p < .001), and MUAMC remained stable. There was a significant improvement in transferrin from 191 +/- 82 to 326 +/- 128 mg/dL (p = .043), and a trend toward improvement in albumin and DHST. Body weight was highly correlated with DXA weight at baseline (r = .997; 95% confidence interval [CI], 0.98 to 1.00; p < .001) and at 3 months (r = .988; 95% CI, 0.93 to 1.00; p <.001). TSF correlated with total fat as measured by DXA at baseline (r = .839; 95% CI, 0.33 to 0.97; p = .009) but not at 3 months (r = .693; 95% CI, -0.02 to 0.94; p = .057). MUAMC correlated with lean soft tissue measured by DXA both at baseline (r = .739; 95% CI 0.07 to 0.95; p = .036) and at 3 months (r = .870; 95% CI, 0.43 to 0.98; p = .005). Physical activity, on a subjective scale of 1 (low activity) to 3 (high activity), improved over the 3-month period from 1.3 +/- 0.5 to 2.2 +/- 0.8 (p = .031). Initial weight gain experienced by malnourished HPN patients is primarily fat. Bone mineral content increases, but lean soft tissue does not change. Overall nutritional status is improved as exhibited by significant improvements in body weight and serum transferrin and a trend toward improvement in albumin and delayed hypersensitivity skin tests.

Exposure to Mycobacterium avium primes the immune system of calves for vaccination with Mycobacterium bovis BCG.

The objective of the investigation was to provide data on how a prior exposure of cattle to Mycobacterium avium, used here as a model of exposure to an environmental mycobacterium, affected the cellular immune response that follows vaccination with Mycobacterium bovis BCG. The assessment of cellular immune responses included lymphocyte proliferation assays, the delayed hypersensitivity skin test and IFN-gamma synthesis in whole blood cultures. One group of calves was inoculated subcutaneously with M. avium followed 12 weeks later by M. bovis-BCG. The other group was vaccinated subcutaneously with BCG alone. Calves previously exposed to M. avium responded more rapidly, as assessed in the in vitro assays, to purified protein derivative (PPD) from M. avium (PPD-A) or M. bovis (PPD-B) than did calves inoculated with BCG only, indicating that the exposure to M. avium had primed the immune response in these calves. Following inoculation of BCG the intensity of the in vitro responses and the delayed hypersensitivity skin test to PPD-A was higher for the M. avium-primed animals while the responses to PPD-B were similar in the M. avium-primed and BCG-only groups. The results are consistent with a model in which prior exposure to environmental mycobacteria does not necessarily inhibit the immune response to the vaccine strain, BCG. They suggest that M. avium infection primes the immune system of calves and that the detection of an immune response specific for M. bovis BCG is masked by reactivity to antigens also present in M. avium.

Relationships between immunity and dietary and serum antioxidants, trace metals, B vitamins, and homocysteine in elderly men and women

It is well known that nutritional status has profound effects on immunity. The compromised cellular immunity that occurs in many otherwise healthy older people includes impaired interleukin-2 (IL-2) production and anergy to skin test antigens. The latter has been associated prospectively with increased mortality in the elderly. We studied dietary and blood concentrations of vitamins A, B6, C and E, folate, β carotene, and zinc and their relationship to delayed hypersensitivity skin test responses (DHST) and serum soluble IL-2 receptor concentrations (IL-2R) in 65 healthy independently-living men and women aged 69.8 ± 7.2 years. Serum concentrations of vitamin B12 and copper and dietary lycopene were also measured. Excluded were subjects who had used vitamin or mineral supplements in the preceding 3 months, since supplementation may improve DHST responses. IL-2R concentrations were positively (p < 0.05) associated with serum concentrations of homocysteine, vitamin B6 and BMI, and negatively associated with serum β-carotene and dietary lycopene. In a multiple regression model, these 5 variables explained 52% of the variability in IL-2R. The percentage of subjects with anergy to a panel of 7 skin test antigens was 25%. DHST responses were negatively associated with T helper cell numbers and serum retinol, T helper cell numbers were positively associated with serum copper, and natural killer cell numbers were positively associated with dietary folate and vitamin B6. Serum homocysteine concentrations were negatively associated with plasma concentrations of folate, and vitamin B12, as well as positively with serum IL-2R. In a multiple regression model, these 3 concentrations explained 27% of the variability in serum homocysteine. The results suggest that IL-2 metabolism may be influenced by several dietary antioxidants and B vitamins including those that alter homocysteine concentrations.

Evidence for antigen-specific immune deviation in patients with acute retinal necrosis.

Because experimental acute retinal necrosis (ARN) induced by herpes simplex virus in mice develops only if mice fail to acquire virus-specific delayed hypersensitivity (DH), although they produce antiviral antibodies (ie, anterior chamber-associated immune deviation), we sought to determine whether a similar inverse correlation exists for patients with varicella-zoster virus (VZV)-induced ARN. Patients with acute, VZV-induced ARN and age-matched control subjects were skin tested with VZV and purified protein derivative antigens to evaluate DH. Varicella-zoster virus-induced ARN was diagnosed using polymerase chain reaction and intraocular antibody quotient. Serum samples were collected and analyzed for anti-VZV and anti-herpes simplex virus antibody titers. Acute retinal necrosis activity was assessed clinically, and DH skin tests were repeated 3 months after onset when ocular recovery had taken place. Whereas controls displayed intense DH when tested with VZV and purified protein derivative antigens, a subset of patients with ARN displayed absent VZV-specific DH (although their purified protein derivative responses were normal). Patients with the most severe ARN had the lowest DH responses to VZV antigens. Serum anti-VZV antibody titers were higher in patients with ARN than in controls, and antiviral titer correlated inversely with the intensity of anti-VZV DH responses. Varicella-zoster virus-specific DH responses were restored in patients who recovered from ARN. Varicella-zoster virus-ARN develops in a setting where DH reactivity to viral antigens is absent, implying that virus-specific DH might ameliorate the severity of ARN. Linking virus-specific DH to vulnerability to ARN in individuals infected with VZV might reveal an underappreciated pathogenic mechanism.

Delayed Hypersensitivity Skin Testing

Many substances, both natural and manufactured, cause inflammation when introduced into living tissue. Some compounds cause a local inflammatory reaction in all exposed individuals and often are called toxic or irritant reactions. Skin testing with other compounds causes an inflammatory response in a limited number of subjects. Those reactions that occur on the basis of specific immune responses are termed hypersensitivity reactions, and the responding individuals are said to be hypersensitive to that antigen. Intradermal skin testing may induce four or more types of cutaneous hypersensitivity reactions in humans 35 : (1) an immediate wheal and flare reaction related to the presence of antigen-specific immunoglobulin E (IgE) in the skin; (2) an IgE-mediated late-phase reaction that follows the wheal and flare, begins several hours after injection, and peaks at 12 to 24 hours; (3) a local vasculitic reaction peaking at 12 to 24 hours that results from the interaction of complement-fixing antibody and antigen at the injection site (Arthus reaction); and (4) a lymphocyte and macrophage-dependent delayed hypersensitivity reaction (DHR). Erythema and induration at the injection site peaks at 48 hours after the injection. The latter reaction is the subject of this article.

Gender and cutaneous leishmaniasis in Colombia

Leishmaniasis in Colombia has traditionally been seen as a health risk for adult males, as they become infected when they enter the vector's biotopes to tap natural resources. National health statistics seem to confirm this theory. However, during field studies, the Program for the Study and Control of Tropical Diseases (PECET) observed both equal proportions of men and women with active leishmaniasis and delayed hypersensitivity skin tests and equal proportions of males and females having had contact with the parasite from early childhood. Several factors that have not been analyzed in depth in Colombia thus far appear to distort the disease's epidemiological pattern in the country, and gender-linked differences in access to health care appear to exist. As a consequence, no relief is provided for this source of human suffering, and socioeconomic repercussions for households are significant. Preventive measures by the Colombian Ministry of Health (MOH) systematically underestimate the magnitude of intra- and peridomiciliary transmission, and female patients are excluded from active case detection. Further research should be devoted to this phenomenon. The MOH should be encouraged to improve leishmaniasis control programs, especially with regard to active case detection, training, and teaching, so that quicker diagnosis can be performed. Meanwhile, the MOH should retrain its health personnel.

Immune dysfunction in refractory sinusitis in a tertiary care setting.

To examine the contribution of the primary immunodeficiency states, which are uncommon in the general population, to refractory sinusitis. We retrospectively reviewed the charts of 316 patients with sinusitis who were referred to the Allergy and Immunology Clinic for immunological evaluation from 1991 to 1997. Of the 316 patients, 79 were selected for further study. Inclusion criteria included at least one sinus surgery and/or sinusitis diagnosed by endoscopy and/or computed tomography (CT) scan at least three times in the previous year. Patients with human immunodeficiency virus (HIV), allergic fungal sinusitis, cystic fibrosis, and primary ciliary dyskinesia were excluded. The results of their immunological evaluation for atopy, T-lymphocyte function, and immunoglobulin levels were examined. The average age of these 79 patients was 44 years (+/- 14.5 standard deviation [SD]). They had, on average, 2.94 (+/- 2.19 SD) previous operations and had mean sinus CT scores (Lund-McKay) of 11.2 (+/- 5.0 SD). Forty of 79 (50.6%) patients had at least one positive result on skin test to an aeroallergen. Delayed hypersensitivity skin testing revealed that 22 of 55 patients (40%) were anergic. Of the 60 patients with in vitro T-lymphocyte function testing, 54.8% showed abnormal proliferation in response to recall antigens, 11.3% had decreased response to alloantigen, and 26.3% demonstrated decreased response to T-cell mitogens. Determination of quantitative immunoglobulins showed low immunoglobulin G in 14 of 78 patients (17.9%), low immunoglobulin A in 13 of 78 (16.7%), and low immunoglobulin M in 4 of 78 (5.1%). Common variable immunodeficiency (CVID) was diagnosed in 9.9% of patients, and selective IgA deficiency was found in 6.2%. This retrospective review reveals an unexpectedly high incidence of immune dysfunction. These results suggest that immunological testing should be an integral part of the evaluation of patients with refractory sinusitis.