Soluble HLA-G and HLA-A,-B,-C serum levels in patients with allergic rhinitis

Background: Allergic rhinitis (AR) is characterized by Th2‐polarized immune response. Soluble HLA (sHLA) molecules play an immunomodulatory activity. So far, however, no study investigated them in AR. Objective: The aim of this study was to evaluate sHLA‐G and sHLA‐A,‐B,‐C serum levels in AR patients with pollen allergy and in a group of healthy controls. Methods: Forty‐nine AR patients were enrolled. A group of healthy nonallergic subjects was considered as control. sHLA‐G and sHLA‐A,‐B,‐C serum levels were determined by immunoenzymatic method. The study was conducted during the winter, such as outside the pollen season. Results: Allergic patients had significantly higher levels of both sHLA‐G (P < 0.0001) and sHLA‐A,‐B,‐C (P = 0.011) molecules than normal controls. Moreover, there was a significant relationship between these two soluble molecules (r = 0.69) in allergic patients. Conclusion: The present study provides the first evidence that both sHLA‐G and sHLA‐A,‐B,‐C serum levels are significantly increased in AR patients with pollen allergy.     

Different serum soluble Fas levels in patients with allergic rhinitis and bronchial asthma

BACKGROUND: The pathogeneses of allergic rhinitis and bronchial asthma are believed to be closely mutually related because of the similar dynamics of allergy-inducing cells and molecules and clinical overlap. In this study, we compared these diseases in the dynamics of cell apoptosis-regulating molecules. METHODS: Allergic rhinitis patients (n=36), bronchial asthma patients (n=22), and healthy subjects (n=32) were subjected to measurement of serum (soluble Fas) (sFas) levels during the stable and attack disease phases by a sandwich enzyme-linked immunosorbent assay. RESULTS: Serum sFas levels in patients with allergic rhinitis during the attack phase were significantly lower (P<0.0001) than those in healthy individuals. There were no differences between them during the attack and stable disease phases. In contrast, serum sFas levels in patients with bronchial asthma during the attack phase were higher (P<0.0005) than those in healthy individuals. Interestingly, the levels during the attack phase were lower (P<0.002) than those during the stable phase. CONCLUSIONS: Our results suggest a different pathogenesis for allergic rhinitis and bronchial asthma at the cell apoptosis-linked step.     

Frequency of acute systemic reactions in patients with allergic rhinitis and asthma treated with sublingual immunotherapy

BACKGROUND: Several studies have demonstrated the efficacy and safety of sublingual immunotherapy in the treatment of respiratory allergy. OBJECTIVE: To determine the frequency of systemic adverse reactions in patients treated with standardized extracts of sublingual immunotherapy. METHODS: Allergic patients with rhinitis with or without asthma and sensitized to at least 1 allergen were included. Increasing doses of standardized allergens were administered until reaching an average dose accumulated of 7,200 U after 26 weeks of treatment. Adverse events were graded according to the European Academy of Allergy and Clinical Immunology immunotherapy position paper. RESULTS: Forty-three patients with a median age of 11 years (interquartile range, 8-20 years) were included. All the patients had allergic rhinitis, and 63% had asthma; they were sensitized mostly to Dermatophagoides pteronyssinus and Dermatophagoides farinae. Four patients (9%) presented with an immediate and 1 (2%) with a late systemic reaction. In total, 7 systemic reactions occurred in 23,154 doses, and all were associated with wheezing or worsening of nasal symptoms (grade 2); in addition, 1 patient had angioedema and urticaria (grade 3). CONCLUSIONS: In this group, systemic reaction frequency was 11.6%, and all were classified as grade 2 or 3. Further assessments in larger samples of patients are required in the context of randomized controlled trials.     

Determination of soluble HLA-G serum levels in patients with adenomyosis and uterine fibroids before and after surgery

Adenomyosis is a benign gynaecological disease caused by the growth of endometrial tissue in the myometrium that affects approximately 30 % of child-bearing-age women. We evaluated the levels of soluble human leukocyte antigen G (sHLA-G) in the serum of patients with adenomyosis before and after treatment. Serum samples of 34 patients with adenomyosis and 31 patients with uterine fibroids were collected before and after the operation and were analysed for sHLA-G levels by ELISA assay. The preoperative levels of serum sHLA-G in the adenomyosis group (28.05 ± 2.466 ng/ml) were significantly higher than those in the uterine fibroid group (18.53 ± 1.435 ng/ml) (P < 0.05). Serum sHLA-G levels in the adenomyosis group showed a decreasing trend at different time points after surgery (28.05 ± 14.38 ng/ml, 18.41 ± 8.34 ng/ml, and 14.45 ± 5.77 ng/ml). Adenomyosis patients who underwent total hysterectomy (n = 20) had a more significant decrease in sHLA-G levels in the early postoperative period (2 days post-operative) than those who underwent partial hysterectomy (n = 14). These results suggest that immunologic dysfunctions may be detected in patients with adenomyosis.     

Relationship between nasal and conjunctival tests in patients with allergic rhinitis

Simultaneous conjunctival and nasal provocation tests, a total of 174 test pairs, were carried out in fifty patients with allergic rhinitis, using serially diluted antigen solutions of birch, Timothy grass and mugwort pollen, as well as cat and dog dander. The nasal mucosa was found to be more sensitive than the conjunctival mucosa in ninety-six test pairs (55 %). This differs from earlier reports. Nasal reaction only was observed in twenty-nine instances (17%). Posterior rhinomanometry was also used to evaluate test reactions, but was found to yield little additional information. In 43 % of nasal provocation tests, which according to other criteria were positive, the rhinomanometric results were negative. Despite a fairly good correlation between the results obtained by nasal and conjunctival challenge, the results point to organ specificity in type I reactions. Provocation tests, if indicated in a thorough allergy evaluation, should be performed in the shock organ. The provocation methods and interpretation of reactions of this study differ from those of earlier reports. Comparison of results is difficult and standardization of methods is needed.     

Biomarkers of immunotherapy response in patients with allergic rhinitis

Introduction: Allergen immunotherapy represents the only disease-modifying therapy available for immunoglobulin E-mediated diseases such as allergic rhinitis and asthma. Allergen immunotherapy induces allergen tolerance by interfering with the immune-pathogenic mechanisms of the allergic response and is potentially able to provide long-term relief of symptoms of allergic rhinitis and asthma and alter the natural course of allergic diseases.

Areas covered: Since allergen immunotherapy (AIT) is actually considered an individualized treatment on patient’s clinical and immunological profile, the identification of specific biomarkers, which may guide diagnosis, management, and predict response to AIT treatment in allergic rhinitis (AR) patients, is essential and is currently an active field of research.

Expert commentary: The identification and validation of biomarkers of successful AIT for AR is an urgent need to definitively establish the role of AIT as a therapeutic tool of personalized medicine.     

HLA-A,-B,-C and-D Antigens in Male Patients with Myasthenia Gravis

HLA-A,-B,-C and-D antigens were determined in 54 male Myasthenia Gravis patients. A significant increase of the B8 antigen frequency was found among patients with an onset of the disease before the age of 35. No significant increase was found among the D antigens. In a combined male and female material with an early age at onset, thymic hyperplasia was correlated to the presence of HLA-B8.     

Polymorphism of intron 4 in HLA-A, -B and -C genes

The sequence database of HLA class I genes focuses on the coding sequences, the exons. Limited information is available on the non-coding sequences of the different class I alleles. In this study we have determined the intron 4 nucleotide sequence of at least one representative of each major allelic group of HLA-A, -B and -C. The intron 4 sequences were determined for 27 HLA-A, 81 HLA-B and 30 HLA-C alleles by allele-specific sequencing, using primers located in adjacent exons and introns. The sequences revealed that the length of intron 4 varies with a minimum of 93 and a maximum of 124 nucleotides as a result of insertions and deletions. There were remarkable similarities and differences within HLA-A, -B and -C, as well as between them. Within HLA-A, a deletion of three nucleotides was detected in several HLA-A alleles. The HLA-B alleles could be divided into two groups with one group having a deletion of 11 nucleotides compared with the second group. Within HLA-C, all Cw*07 alleles showed remarkable differences with the other Cw alleles. Cw*07 had an insertion of three nucleotides, shared only by the Cw*17 group. Moreover, Cw*07 was found to have an aberrant nucleotide sequence. Differences between HLA-A, -B and -C alleles were also observed. Remarkable was the deletion of 20 nucleotides in all HLA-A and -B alleles compared with HLA-C, whereas the HLA-A alleles showed an insertion of one nucleotide and a deletion of three nucleotides compared with HLA-B and -C. Furthermore, 32 different polymorphic positions were detected between HLA-A, -B and -C.     

Cost-effectiveness of specific subcutaneous immunotherapy in patients with allergic rhinitis and allergic asthma

BACKGROUND: Specific immunotherapy is the only potentially curative treatment in patients with allergic rhinitis and allergic asthma. Health economic evaluations on this treatment, particularly in a German context, are sparse. OBJECTIVE: To evaluate the cost-effectiveness of specific subcutaneous immunotherapy (SCIT) in addition to symptomatic treatment (ST) compared with ST alone in a German health care setting. METHODS: The analysis was performed as a health economic model calculation based on Markov models. In addition, we performed a concomitant expert board composed of allergy experts in pediatrics, dermatology, pneumology, and otolaryngology. The primary perspective of the study was societal. Additional sensitivity analyses were performed to prove our results for robustness. RESULTS: The SCIT and ST combination was associated with annual cost savings of Euro140 per patient. After 10 years of disease duration, SCIT and ST reach the breakeven point. The overall incremental cost-effectiveness ratio (ICER) was Euro-19,787 per quality-adjusted life-year (QALY), with a range that depended on patient age (adults, Euro-22,196; adolescents, Euro-14,747; children, Euro-12,750). From a third-party payer's perspective, SCIT was associated with slightly additional costs. Thus, the resulting ICER was Euro8,308 per QALY for all patients. CONCLUSIONS: Additional SCIT was associated with improved medical outcomes and cost savings compared with symptomatic treatment alone according to a societal perspective. Taking a European accepted ICER threshold of up to Euro50,000 per QALY into account, additional SCIT is considered clearly cost-effective compared with routine care in Germany. The degree of cost-effectiveness is strongly affected by costs related to SCIT and the target population receiving such treatment.     

Elevated soluble tumor necrosis factor receptor levels in seasonal allergic rhinitis patients

In this study, we examined the symptom scores and tumor necrosis factor-alpha (TNF-alpha), p55 soluble tumor necrosis factor receptor (sTNFR1), and p75 soluble tumor necrosis factor receptor (sTNFR2) levels in the sera and nasal epithelial lining fluids (ELF) of 20 patients with Japanese cedar pollinosis from the pre- to the postseason period, and compared the results with those of 10 nonallergic control subjects. The symptom scores of the allergic subjects were significantly (P<0.01) higher than those of the nonallergic subjects during the early stage and mid-stage of the season. There were no statistical differences between the allergic and nonallergic subjects in the TNF-alpha levels in sera and ELF from the pre- to the postseason. In the allergic subjects, however, the levels of sTNFR1 and sTNFR2 in ELF were significantly elevated during the early stage (P<0.05) and mid-stage (P<0.01) of the season, whereas those in sera did not change from the pre- to the post-season period. The levels of TNF-alpha in ELF were more than 10 times higher than those in sera, whereas the levels of sTNFR1 and sTNFR2 in ELF were less than half of those in sera in the allergic and nonallergic subjects. These results suggest that sTNFR1 and sTNFR2 may play a role in the pathogenesis of nasal allergic reaction.     

Increase in serum levels of autoantibodies after attack of seasonal allergic rhinitis in patients with Graves' disease

BACKGROUND: The prevalence of allergic disease is increasing worldwide, but its influence on the clinical course of autoimmune diseases is unknown. OBJECTIVE: The purpose of this study was to assess the effect of seasonal allergic rhinitis on the clinical course of Graves' disease, which has been considered a Th2-dominant autoimmune disease. METHODS: Ten patients with Graves' disease, who were considered to be in a state of remission or near remission, were serially examined for 18 months starting from August. Five of them had seasonal allergic rhinitis due to Japanese cedar pollen, and the remaining patients had no such allergic disorders. Peripheral eosinophil counts, serum concentrations of cedar-pollen-specific IgE, anti-TSH-receptor antibody, anti-thyroid-peroxidase antibody and antithyroglobulin antibody were assessed at 2- to 4-month intervals. Serum thyroid hormones and TSH levels were also measured to evaluate disease activity. RESULTS: All patients with pollinosis had attacks of allergic rhinitis caused by cedar pollen in early March. Subsequently, peripheral eosinophil counts, pollen-specific IgE activity and serum levels of anti-thyroid-peroxidase and antithyroglobulin autoantibodies markedly increased. Serum levels of anti-TSH-receptor antibody increased in 3 patients in association with an increase in serum thyroid hormones but were always negative in 2 patients. The control patients without pollinosis showed no consistent change of these parameters. CONCLUSIONS: Seasonal allergic rhinitis aggravated the clinical course of Graves' disease and induced an increase in serum antithyroid autoantibody concentrations as well as an increase in pollen-specific IgE concentration. These data suggest that environmental antigens induce not only local allergic reactions, but also stimulate thyroid immune reactions toward Th2 proliferation, and finally aggravate Th2-dependent autoimmune thyroid disease.     

Behavior of non-classical soluble HLA class G antigens in human immunodeficiency virus 1-infected patients before and after HAART: Comparison with classical soluble HLA-A, -B, -C antigens and potential role in immune-reconstitution

We have reported that serum level of soluble HLA-A, -B, -C (sHLA-A,-B,-C) antigens is elevated in HIV-infected subjects and decreases after antiretroviral therapy (HAART). In this study, we measured the levels of soluble HLA-G (sHLA-G) antigens in a cohort of HIV-infected patients before and during HAART. sHLA-G and sHLA-A, -B, -C levels were significantly elevated in HIV-infected subjects as compared with controls before antiretroviral treatment and significantly decreased after 36 months of HAART. sHLA-G levels were correlated with sHLA-A, -B, -C levels, the decrease of plasma HIV-RNA level, the increase of CD4+ T-lymphocyte number and the decrease of CD8+ T-lymphocyte number. These results suggest that the measurement of sHLA-G and sHLA-A, -B, -C antigen serum levels might represent a useful surrogate marker to monitor virological response and immune reconstitution in HIV-positive subjects undergoing HAART treatment.     

Association study between HLA-A, -B, -C, -DRB1 alleles and Psoriatic arthritis in southern France

Psoriatic arthritis (PsA) is a type of inflammatory arthritis associated with psoriasis. HLA association studies performed in northern Europe, comparing patients with control populations, have shown that the highest risk for PsA is carried by HLA-C*06, HLA-B*57 and HLA-B*27 alleles.This retrospective association study compared HLA-A, -B, -C, and -DR alleles of 500 patients from southern France, who fulfilled the CASPAR criteria for Psoriatic Arthritis (PsA), with 2346 controls from healthy blood donors, using the chi-square test.We classified PsA patients into three different subgroups according to disease: purely axial, purely peripheral and combined axial and peripheral. The ‘axial’ subgroup was associated with HLA-B*27 (OR = 16.3, p = 2.7 × 10^?28) and its haplotypes: HLA- B*27-C*01 (OR = 12.4, p = 1.7 × 10^?12) and HLA-B*27-C*02 (OR = 8.7, p = 10 × 10^?9). The ‘axial and peripheral’ and the ‘peripheral’ subgroups were associated with HLA-C*06 (respectively OR = 1.5, p = 3.6 × 10^?10 and OR = 2.4, p = 3.6 × 10^?12) and its haplotypes HLA-C*06-B*13 (respectively OR = 2.4, p = 1.2 × 10^?6 and OR = 2.8, p = 6.4 × 10^?11).This association study on a southern French PsA cohort identifies HLA-C*06 as a marker for peripheral PsA and HLA-B*27 as a marker for purely axial PsA.     

Study of HLA-A, -B, -C, -DRB1 and -DQB1 polymorphisms in COVID-19 patients

BackgroundHuman leukocyte antigen (HLA) plays an important role in immune responses to infections, especially in the development of acquired immunity. Given the high degree of polymorphisms that HLA molecules present, some will be more or less effective in controlling SARS-CoV-2 infection. We wanted to analyze whether certain polymorphisms may be involved in the protection or susceptibility to COVID-19.MethodsWe studied the polymorphisms in HLA class I (HLA-A, -B and -C) and II (HLA-DRB1 and HLA-DQB1) molecules in 450 patients who required hospitalization for COVID-19, creating one of the largest HLA-typed patient cohort to date.ResultsOur results show that there is no relationship between HLA polymorphisms or haplotypes and susceptibility or protection to COVID-19.ConclusionOur results may contribute to resolve the contradictory data on the role of HLA polymorphisms in COVID-19 infection.     

Relationship between nasal hyperreactivity, mediators and eosinophils in patients with perennial allergic rhinitis and controls

Background In perennial allergic rhinitis, patients are almost daily exposed to aeroallergens. This ongoing allergic reaction results in increased sensitivity to allergens and non-specific stimuli. It is generally known that inflammatory cells and mediators are involved in the pathogenesis of the allergic reaction. Objectives To study the relationship between nasal hyperreactivity and nasal inflammation during natural allergen exposure. Methods In 48 patients with perennial allergic rhinitis and in 11 volunteers a nasal brush, a nasal lavage and a histamine challenge were performed. Nasal inflammation was estimated by the number of eosinophils, levels of albumin, tryptase, prostaglandin D₂ (PGD₂), eosinophil cationic protein (ECP) and leukotriene C₄/D₄/E₄ (LTC₄/D₄/E₄). Results In contrast to PGD₂ and tryptase, eosinophils (1.9 vs 0%, P = 0.0023), LTC₄/ D₄/E₄ (17.51 vs 1.43pg/mL, P= 0.0001) and albumin (8.61 vs 2.37mg/mL, P= 0.0008) were significantly increased in rhinitis patients as compared with controls. Patients also showed increased responses to nasal histamine challenge assessed using a composite symptom score (21.5 vs 4 points, P=0.0001). The nasal response to histamine was weakly correlated with the total number of eosinophils in the cytospin (correlation coefficient r=0.38, P= 0.009). Conclusion Nasal hyperreactivity is correlated with the percentage of eosinophils in patients with perennial rhinitis. The patients' mediator profiles suggest that eosinophils are important in the ongoing allergic reaction and nasal hyperreactivity.