Case report: Human seminal plasma allergy diagnosis for a woman with unexplained infertility.

Background: Infertility is a pressing global public health concern, affecting millions worldwide, and the diagnosis of unexplained infertility poses particular challenges. Human seminal plasma allergy, a rarely diagnosed type I hypersensitivity reaction, emerges as a potential but often overlooked contributor to female infertility. With rare reported cases globally, the condition's low awareness and insufficient differential diagnosis may mask its actual prevalence. Case report: This case report presents the clinical case of a 29-year-old woman with unexplained infertility who underwent two unsuccessful IVF procedures and was subsequently diagnosed with human seminal plasma allergy. The patient, known for bronchial asthma and allergic rhinitis exacerbated by inhalant allergens, exhibited eosinophilia and a history of local allergy symptoms (burning sensation, vulvar pruritus, edema, and general discomfort) as well as sneezing and nasal congestion following unprotected intercourse-symptoms compatible with human seminal plasma allergy. Molecular allergy diagnostics revealed pronounced sensitization to dust mites and Can f 5, a canine-specific allergen. A positive skin prick test using her partner's sperm confirmed the diagnosis of human seminal plasma allergy. The patient's medical history also includes mild endometriosis, raising questions about the interplay between allergic conditions and fertility. Treatment options such as barrier contraception, antihistamine therapy, and sperm desensitization are discussed. Conclusion: Highlighting the need for increased awareness among healthcare professionals, this case emphasizes the significance of reporting and sharing clinical experiences to enhance our understanding of this rare condition. As researchers continue to accumulate relevant information, a more comprehensive understanding of human seminal plasma allergy and its potential impact on female fertility will contribute to improved diagnostic protocols and expanded treatment options. This case report contributes to the growing body of knowledge surrounding this rare allergy, serving as a reminder of possible intricate relationships between allergic conditions and reproductive health.

Sensitization to molecular dog allergens in an adult population: Results from the West Sweden Asthma Study.

BACKGROUND: As the prevalence of dog allergy rises, component resolved diagnosis might improve the diagnosis, understanding of the clinical outcomes and the effectiveness of immunotherapy. Considering the paucity of data in adults, the current study characterized the patterns of sensitization to dog molecular allergens in an adult population. METHODS: Data were derived from the West Sweden Asthma Study, a population-based and representative sample of adults from western Sweden. Of the 2006 subjects clinically examined, 313 participants sensitized to whole dog allergen extract were measured for specific immunoglobulin E (sIgE) levels to Can f 1, Can f 2, Can f 3, Can f 4, Can f 5 and Can f 6 using ImmunoCAP™. Polysensitization was defined as sensitization to ≥3 components. Overlapping sensitization was defined as having concomitant sensitization to at least two dog molecular allergen families (lipocalin, albumin or prostatic kallikrein). RESULTS: Of 313, 218 (70%) subjects tested positive to at least one dog allergen component. Sensitization to Can f 1 (43%) was the most common, followed by Can f 5 (33%) among molecular allergens, while sensitization to lipocalins (56%) was the most common among component families. Polysensitization was found in 22% of all participants and was more common in participants with than in those without asthma. Subjects with asthma were less likely to be monosensitized to Can f 5 than those without asthma. Subjects with asthma had higher IgE levels of Can f 3, Can f 4 and Can f 6 than those without asthma. Overlapping sensitizations also differed between those with asthma and allergic rhinitis and those without. CONCLUSION: Increased knowledge about the sensitization patterns of dog allergen components can aid in defining their role in asthma and rhinitis. In complex clinical cases of dog allergy, a detailed analysis of dog allergen components can provide additional information on the nature of sensitization.

Experimental Research Models to Assess the Cross-Reactivity between Can f 5 and Human PSA-Two Different Perspectives.

The similarity in antigenic structures, including the degree of correspondence between the amino acid sequence and the spatial structure, is not always reflected in the actual cross-reactivity of allergens. Inhibition tests appear to be an invaluable tool for assessing potential cross-reactivity between allergens under natural conditions. In this publication, we present two experimental models of inhibition tests: solid phase (SP-IT) and liquid phase (LP-IT). As an exemplary research model, we used the cross-reactivity between human PSA and anti-Can f 5 IgE antibodies. We performed an SP-IT model using a microplate coated with human PSA. The LP-IT model was based on mixing anti-Can f 5 IgE positive serum with a material containing human PSA. Anti-Can f 5 IgE and PSA concentrations before and after inhibition were measured to evaluate inhibition effectiveness. The results of the performed experiments showed that both proposed models of inhibition tests are an effective tools for studying cross-reactive relationships between antigens. In the SP-IT, the concentration of anti-Can f 5 decreased by 21.6% and, in the LP-IT, it decreased by 34.51%. In turn, the PSA concentration in the SP-IT decreased by 11.25% and, in the LP-IT, it decreased by 15.49%. In conclusion, both the SP-IT and the LP-IT seem to be effective tools for assessing the actual cross-reactivity between different allergens.

Immunological mechanisms involved in the human response to a dog dander allergoid.

BACKGROUND: Dog allergens are a common cause of allergic sensitisation and trigger respiratory symptoms worldwide. However, clinical evidence regarding dog immunotherapy is limited. Therefore, the aim of this study was to analyse the immunomodulatory properties of a new allergoid from dog dander, thereby deepening the understanding of the molecular mechanisms involved in the reestablishment of the tolerogenic response. METHODS: Three independent batches of dog dander native and allergoid allergen extracts were manufactured and characterised. Allergenic profiles were analysed by the identification of all dog allergens and quantification of the major allergens Can f 1 and Can f 5. The allergenicity profile of the allergoid was studied using biological potency and basophil activation tests. In vitro immunomodulatory parameters was evaluated as the capacity of the allergoid to induce IgG antibodies that block IgE binding to the allergen and cytokine promotion (IFN-γ, IL-4, IL-6, IL-10, IL-13, and TNF-α) in PBMCs from allergic donors. RESULTS: The presence of all dog allergens, including Can f 1 and Can f 5, was confirmed in both types of extracts. The new allergoid showed a low IgE binding capacity, which significantly affected the activation of effector cells, such as basophils. The IgG antibodies induced by the allergoid in rabbits blocked human IgE binding epitopes on the dog native extract and induced Th1 and Treg responses by increasing IFN-γ and IL-10 levels in PBMCs from allergic donors. CONCLUSION: This new dog dander allergoid containing Can f 1 and Can f 5 showed a low capacity to bind IgE and to activate basophils in dog allergic patients. Furthermore, it showed potent activation of Th1 mediators and induction of tolerance through Treg activation. This allergoid could offer a safer profile than the native extract and could be an effective immunotherapy treatment for dog allergic patients.

Single-cell characterization of dog allergen-specific T cells reveals TH2 heterogeneity in allergic individuals.

BACKGROUND: Allergen-specific type 2 CD4+ TH2 cells are critically involved in the pathogenesis of IgE-mediated allergic diseases. However, the heterogeneity of the TH2 response has only recently been appreciated. OBJECTIVE: We sought to characterize at the single-cell level the ex vivo phenotype, transcriptomic profile, and T-cell receptor (TCR) repertoire of circulating CD4+ T cells specific to the major dog allergens Can f 1, Can f 4, and Can f 5 in subjects with and without dog allergy. METHODS: Dog allergen-specific memory CD4+ T cells were detected ex vivo by flow cytometry using a CD154-based enrichment assay and single-cell sorted for targeted gene expression analysis and TCR sequencing. RESULTS: Dog allergen-specific T-cell responses in allergic subjects were dominantly of TH2 type. TH2 cells could be phenotypically further divided into 3 subsets, which consisted of TH2-like (CCR6-CXCR3-CRTH2-), TH2 (CCR6-CXCR3-CRTH2+CD161-), and TH2A (CCR6-CXCR3-CRTH2+CD161+CD27-) cells. All these subsets were nonexistent within the allergen-specific T-cell repertoire of healthy subjects. Single-cell transcriptomic profiling confirmed the TH2-biased signature in allergen-specific T cells from allergic subjects and revealed a TH1/TH17 signature in nonallergic subjects. TCR repertoire analyses showed that dog allergen-specific T cells were diverse and allergic subjects demonstrated less clonality compared to nonallergic donors. Finally, TCR and transcriptomic analyses revealed a close relationship between TH2-like, TH2, and TH2A cells, with the last ones representing the most terminally differentiated and highly polarized subtype. CONCLUSIONS: Our study demonstrates heterogeneity within allergen-specific TH2 cells at the single-cell level. The results may be utilized for improving immune monitoring after allergen immunotherapy and for designing targeted immunomodulatory approaches.

Lessons from peculiar cases of anaphylaxis: why allergists should be prepared for the unexpected.

Summary: Anaphylaxis is the most severe systemic hypersensitivity reaction, it can be caused by a number of well identified triggers such as foods, drugs, stinging insects and facilitated by predisposing clinical conditions. However, sometimes anaphylaxis shows up with uncommon or peculiar characteristics which could delay diagnosis and therapeutic treatment. In this report we aimed to describe less accounted / difficult-to-approach shapes of anaphylaxis to facilitate clinicians to suspect these severe reactions even in uncommon conditions. We choose to present data on anaphylaxis regarding simulation, mode of exposure to sensitizing agents, pregnancy, exposure to animals, intimate behaviour, psychological stress and other situations.

Analysis of allergen profile in patients sensitized to canine allergen and potential Can f 5 cross-reactivity with human PSA.

Can f 5 allergy and possible cross-reactivity with human semen in which there are significant amounts of prostate-specific antigen (PSA) are particularly interesting aspects of allergy to dog. The objective of the study was to confirm cross-reactivity between human PSA and Can f 5 in a study of canine sensitised women. A total of 100 women (aged 18-73, 41 on average) with a positive history of animal fur allergy or positive skin prick tests to canine allergens were selected. Levels of Immunoglobulin E (IgE) specific to Can f 1, Can f 2, Can f 3, Can f 5 were determined. Patients with increased concentration of sIgE Can f 5 were selected for further inhibition testing using polystyrene microplate ELISA test coated with human PSA. In the studied population, allergy to Can f 5 dominated (52.3% of patients with increased concentration of canine-specific IgE were allergic to this allergenic component). In all analyzed cases, the concentration of IgE Can f 5 decreased after incubation on the ELISA plate coated with human PSA. The minimum decrease in concentration was 10.44%, the maximum was 37.73%, the average decrease was 21.6%. No statistically significant influence of the presence or absence of allergenic sIgE Can f 5 in blood serum on the occurrence of symptoms after intercourse was found. The study confirmed the moderate ability of Can f 5 to cross-react with human PSA sIgE, which may be clinically significant in some women. At the same time, symptoms of an allergy to male semen do not constitute a typical clinical presentation of allergy to Can f 5.

Children Monosensitized to Can f 5 Show Different Reactions to Male and Female Dog Allergen Extract Provocation: A Randomized Controlled Trial.

BACKGROUND: Dog dander consists of several allergenic molecules including Can f 5, which is a protein expressed in the prostate of male dogs. OBJECTIVE: To investigate whether children monosensitized to Can f 5 show different reactions to provocation tests with male versus female dog dander in a double-blind randomized clinical trial. METHODS: Twenty-two children (15-18 years) with a history of dog sensitization were enrolled from the COpenhagen Prospective Studies on Asthma in Childhood2000 mother-child cohort. Skin prick test, specific IgE levels to dog dander (e5), and dog components Can f 1, 2, 3, and 5 were first assessed. We subsequently performed skin prick test and conjunctival allergen provocation test using dog dander collected separately from male and female dogs. RESULTS: Seven of the 22 children were monosensitized to Can f 5. Eight were sensitized to a mix of the dog components, and 7 were no longer sensitized to dog. Of the children monosensitized to Can f 5, all had a positive skin prick test result to male dog extract and 1 of 7 was also positive to female dog extract (P = .01). Furthermore, 5 of 7 had a positive conjunctival allergen provocation test result to male dog extract and 1 of 7 also reacted to the female dog extract (P = .03). There was no difference between reactions to male and female dog extract provocation in children sensitized to a mix of the dog components. CONCLUSIONS: Children monosensitized to Can f 5 show different reactions to male and female dog extract provocation using both skin prick test and conjunctival allergen provocation test, suggesting tolerance to female dogs.

Frequency of allergic sensitization to Can f 5 in North East Italy. An analysis of 1403 ISACs 112 (Component Resolved Diagnosis) collected retrospectively.

Summary: Recent studies have shown the increasing relevance of allergic sensitization to Can f 5, a prostatic kallicrein expressed in the prostate and detectable only in male dogs. The aim of the present study was to establish the frequency, level of sensitization and association with other dog allergens of Can f 5, as assessed by Component Resolved Diagnosis (CRD- ISAC 112, ThermoFisher Scientific, Uppsala, Sweden), in North East Italy. A total of 1403 CRD ISAC 112 were examined retrospectively. Five-hundred twenty subjects (37 %) had a positive IgE response to at least one of the available animal allergens. Among these 520 subjects, 268 (51.5 %) showed at least one sensitization to dog allergens. Among dog-sensitized individuals, 183 (69.02%) showed IgE against Can f 5, and 106 (57.92%) were sensitized exclusively against Can f 5. The average Can f 5 specific IgE was 8.810 ISU-E, with 77.6 % of individuals showing medium or high values of specific IgE according to manufacturer's specifications. In conclusions, our data confirmed that there is a high number of sensitized patients to Can f 5, which have a high degree of allergic sensitization. These results should be taken into account by allergists managing dog allergic patients. In fact, clinical consequences of this sensitization regard respiratory allergy (burden of rhinitis/asthma), systemic reactions (anaphylaxis during sexual intercourse from cross-reaction with human prostatic antigen), allergen immunotherapy-AIT (likely ineffective in patients with exclusive sensitization), and preventive measures (possibility to own a female dog and a likely reduction of allergen passive transport). Further studies are needed to better explore these aspects in "real life".

Molecular allergy diagnostics refine characterization of children sensitized to dog dander.

BACKGROUND: Sensitization to dog dander is an important risk factor for rhinoconjunctivitis and asthma but is not sufficient for diagnosing dog allergy. Molecular allergy diagnostics offer new opportunities for refined characterization. OBJECTIVES: We sought to study the association between sensitization to all presently known dog allergen components and clinical symptoms of dog allergy in children evaluated by using nasal provocation tests (NPTs). METHODS: Sixty children (age, 10-18 years) sensitized to dog dander extract underwent NPTs with dog dander extract. Measurement of IgE levels to dog dander and to Can f 1, Can f 2, Can f 3, and Can f 5 was performed with ImmunoCAP, and measurement of IgE levels to Can f 4 and Can f 6 was performed with streptavidin ImmunoCAP. An IgE level of 0.1 kUA/L or greater was considered positive. RESULTS: There was an association between sensitization to an increasing number of dog allergen components and a positive nasal challenge result (P = .01). Sensitization to lipocalins (odds ratio [OR], 6.0; 95% CI, 1.04-34.5), in particular Can f 4 (OR, 6.80; 95% CI 1.84-25.2) and Can f 6 (OR, 5.69; 95% CI, 1.59-20.8), was associated with a positive NPT result. Monosensitization to Can f 5 was related to a negative NPT result (OR, 5.78; 95% CI, 1.01-33.0). CONCLUSION: Sensitization to an increasing number of dog allergen components and to lipocalins is associated with dog allergy. Monosensitization to Can f 5 should not be regarded primarily as a marker for dog allergy.

Dog allergy: can a prevalent or exclusive sensitization to Can f 5 be considered a lucky or negative event in real life?

Summary: Recent studies have shown the increasing relevance of allergic sensitization to Can f 5 (a prostatic kallikrein), which is an androgen-regulated protein expressed in the prostate and detectable only in male dogs. Can f 5 can be a prevalent or exclusive sensitizing agent in a considerable percentage of dog-allergic patients. Its specific allergenic characteristics are able to induce possible negative as well as positive clinical effects in individuals sensitized to dogs. In the present article we pointed out the possible pros or cons of sensitization to this allergen in real life. Further studies should be carried out to correctly assess some peculiar characteristics of Can f 5, in order to support the most of positive aspects and remedy at best the negative effects.

Critical aspects in dog allergen immunotherapy (DAI). May Component Resolved Diagnosis (CRD) play a role in predicting the efficacy?

We hypothesize that a pivotal condition determining the efficacy of dog allergen immunotherapy (DAI) might be the mono-sensitization to dog lipocalins (Can f 1-2) in individuals not directly or indirectly exposed to other furry animals. In fact, the concomitant sensitization to lipocalins and/or albumins, especially in those patients directly exposed to furry animals, may potentially stimulate patient's airways by inducing persistent inflammation and, thus, clinical symptoms. In these conditions, it is likely that DAI alone could be inadequate to reduce airway inflammation mediated by inhalation of dog allergens in patients with simultaneous exposure to other furry animals. Can f 5 has been found as exclusive allergen in about one third of dog-sensitized individuals. Considering the presence of different allergenic materials in extract of mammalian origin, it is evident that a standard DAI is not likely to be effective in Can f 5 prevalent or mono-sensitized individuals. Moreover, we would underline the need of collecting detailed information on the possible exposures to furry animals (other than the common pets), an information that usually is neglected in clinical practice. Furthermore, a detailed clinical history exploring the real significance of dog sensitization (mono or poly-sensitization, induction of clinical symptoms after exposure etc.) should be performed before prescribing DAI. In some patients, with potential high susceptibility to animal allergens, the use of CRD is essential to verify the presence of concomitant allergic sensitization to lipocalins and/or albumins belonging to other furry animals. The availability of CRD introduced the possibility of a better targeted prescription of DAI because it might be useful for point out the primary allergens and for the exclusion of cross-reactive ones.

Human memory CD4+ T cell response to the major dog allergen Can f 5, prostatic kallikrein.

BACKGROUND: Human CD4+ T cell responses to important animal allergens are still insufficiently understood. OBJECTIVE: To comprehensively characterize in vitro and ex vivo the peripheral blood memory CD4+ T cell responses of subjects with and without allergy to the major dog allergen Can f 5, the only known animal allergen in the kallikrein family of proteins. METHODS: Can f 5-specific memory CD4+ T cell lines (TCLs) were established from the peripheral blood of 12 subjects with and 12 subjects without allergy to Can f 5 and characterized for their functional and phenotypic properties. The results were evaluated with those obtained ex vivo with a novel CD154 enrichment method. The epitopes recognized by the Can f 5-specific TCLs were determined with 72 overlapping 16-mer peptides covering the sequence of the allergen. RESULTS: Can f 5-specific TCLs were obtained at about tenfold higher frequency from allergic than from non-allergic subjects. Functionally, the TCLs of allergic subjects displayed a Th2-biased cytokine phenotype and increased T cell receptor avidity, whereas the TCLs of non-allergic subjects displayed a Th1-/Th0-biased cytokine phenotype and lower TCR avidity. The higher frequency and the Th2 phenotype of Can f 5-specific memory CD4+ T cells in allergic subjects were confirmed by the CD154 enrichment method ex vivo. Six distinct T cell epitope regions of Can f 5 were predominantly recognized by the TCLs from allergic subjects. CONCLUSIONS AND CLINICAL RELEVANCE: Can f 5-specific memory CD4+ T cell responses differ considerably between subjects with and without allergy, as assessed by both in vitro and ex vivo approaches. Peptides containing the dominant T cell epitopes of Can f 5 can be employed for developing peptide-based immunotherapy for dog allergy.

Sensitization to cat and dog allergen molecules in childhood and prediction of symptoms of cat and dog allergy in adolescence: A BAMSE/MeDALL study.

BACKGROUND: Sensitization to individual cat and dog allergen molecules can contribute differently to development of allergy to these animals. OBJECTIVE: We sought to investigate the association between sensitization patterns to cat and dog allergen molecules during childhood and symptoms to these furry animals up to age 16 years. METHODS: Data from 779 randomly collected children from the Barn/Children Allergy/Asthma Milieu Stockholm Epidemiologic birth cohort at 4, 8, and 16 years were used. IgE levels to cat and dog were determined by using ImmunoCAP, and levels to allergen molecules were determined by using an allergen chip based on ISAC technology (Mechanisms for the Development of Allergy chip). Allergy was defined as reported rhinitis, conjunctivitis, or asthma at exposure to cat or dog. RESULTS: Cross-sectionally, IgE to Fel d 1 and cat extract had similar positive predictive values for cat allergy. IgE to Can f 1 showed a higher positive predictive value for dog allergy than dog extract IgE. Sensitizations to Fel d 1 and Can f 1 in childhood were significantly associated with symptoms to cat or dog at age 16 years. Polysensitization to 3 or more allergen molecules from cat or dog was a better longitudinal predictor of cat or dog symptoms than results of IgE tests with cat or dog allergen extract, respectively. Cross-sectionally, cat/dog-polysensitized children had higher IgE levels and more frequent symptoms to cat and dog than monosensitized children. CONCLUSIONS: Sensitization to Fel d 1 and Can f 1 in childhood and polysensitization to either cat or dog allergen molecules predict cat and dog allergy cross-sectionally and longitudinally significantly better than IgE to cat or dog extract.