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Background: This study aimed to investigate the diagnostic performance of combined computed tomography (CT) and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for predicting histologic invasiveness of pure ground-glass nodules (pGGNs). Methods: The study analyzed 91 patients who underwent resection of pGGNs and examined the correlation of pathologic invasiveness with preoperative CT and FDG PET findings. Results: Overall, 24, 36, and 31 patients had adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAD), respectively. Compared with AIS and MIA, IAD was significantly correlated with larger CT size (P = .001), maximum CT value (P = .026), and high maximum standardized uptake value (SUVmax; P < .001). Multivariable logistic analyses revealed that CT size (odds ratio [OR], 3.848; P = .019) and SUVmax (OR, 4.968; P = .009) were independent predictors of histologic invasiveness. Receiver operating characteristic curve analysis revealed that a cutoff CT size value of 18 mm predicted histologic invasiveness with a sensitivity and specificity of 65% and 80%, respectively; similarly, a cutoff SUVmax value of 1.5 predicted histologic invasiveness with a sensitivity and specificity of 61% and 90%, respectively. Of 20 lesions with CT size ≥18 mm and SUVmax ≥1.5, 16 (80%) were IAD. Of 54 lesions with CT size

Abstract Background Although there are great expectations regarding the use of tumor‐infiltrating lymphocytes (TILs) to predict effects of immunotherapies and prognosis, knowledge about TILs remains insufficient for clinical application. Methods We objectively investigated the prognostic significance of tumor‐infiltrating CD8 + lymphocytes (CD8 + TILs) in squamous cell lung cancer (SQ‐LC). Among patients who underwent surgical resection of SQ‐LC in 2011–2017, 100 patients with pathological stage IA3‐III were immunohistochemically studied to evaluate CD8 + TILs in the tumor stroma and parenchyma. The impact of CD8 + TILs on relapse‐free survival was analyzed using a Kaplan–Meier survival analysis and multivariate analyses using Fine‐Gray and Cox proportional hazards models. Results The multivariate analysis showed that large and small numbers, but not intermediate numbers, of CD8 + TILs in the tumor stroma may be related to a more favorable prognosis (small vs. intermediate: HR, 0.64; 95% CI: 0.29–1.41, p = 0.27; large vs. intermediate: HR, 0.48; 95% CI: 0.21–1.09, p = 0.08). In contrast, a large number of CD8 + TILs in the tumor parenchyma was associated with a poor prognosis (HR, 2.60; 95% CI: 0.91–7.42, p = 0.075). An exploratory analysis showed a potentially strong association between an extremely large number of CD8 + TILs in the tumor parenchyma and a poor prognosis, even with a large number of CD8 + TILs in the tumor stroma. Conclusion Our study provided partial but important information on the significance of CD8 + TILs in SQ‐LC. To use CD8 + TILs as biomarkers, a better understanding of CD8 + TILs as well as other important components in the tumor microenvironment and the inflammatory phenotypes they form may be needed.

Some food allergic patients who have undergone oral immunotherapy develop exercise-induced allergic reactions on desensitization (EIARDs). This study investigated basophil activation status during the exercise provocation test (EPT) performed to diagnose EIARD. EPT was performed on 20 participants, and in vivo basophil activation status was analyzed using activation markers CD203c and CD63. The results showed that there was no significant difference between EPT-positive and negative subjects for basophil activation status throughout EPT. Consequently, in vivo basophil activation after ingestion of the causative food may not be associated with EIARDs. New tests are desired for predicting EIARDs.

Abstract Background The effectiveness of local therapy has been reported in patients with oligo‐recurrence of non‐small cell lung cancer (NSCLC), a metachronous recurrence with a limited number of recurrences, which can be treated with local therapy. Conversely, remarkable progress has been made in systemic therapy for NSCLC with the advent of molecular targeted therapy. In particular, epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) are very effective in the treatment of EGFR‐mutated NSCLC. There is currently no consensus on treatment for oligo‐recurrence of EGFR‐mutated NSCLC. Methods From 2004 to 2014, 811 patients underwent complete resection for NSCLC at Kitasato University Hospital and, of these, 244 patients developed recurrence. Oligo‐recurrence was defined as the presence of two or less recurrent lesions, and 34 patients presented with EGFR‐mutated oligo‐recurrence. Results We retrospectively examined and compared the effects of EGFR‐TKIs with those of radical local therapy in patients with oligo‐recurrent EGFR‐mutated NSCLC. The five‐year post‐recurrence survival (PRS) rates of patients with EGFR‐mutated oligo‐recurrence who received radical local therapy (n = 23) and those who did not (n = 11) were 59.4 and 45.5%, respectively (p = 0.777). Multivariate analysis revealed no favorable prognostic factors associated with prolonged PRS, and radical local therapies did not improve PRS in patients with oligo‐recurrence (p = 0.551). Conclusion Radical local therapy did not affect PRS in patients with oligo‐recurrent EGFR‐mutated NSCLC. Even in cases of oligo‐recurrence, the administration of local therapy in patients with EGFR‐mutated NSCLC might be carefully considered.

Abstract Background The Rosaceae family includes fruits, such as peach, apple, Japanese apricot, cherry (Prunoideae subfamily), and strawberry (Rosoideae subfamily). The allergens responsible for Rosaceae fruit allergies have been reported to include Bet v 1 and profilin, which mainly cause oral symptoms, and lipid transfer protein (LTP). Recently, gibberellin-regulated protein (GRP) has been identified as an allergen that induces generalized symptoms in peach-, orange-, and plum-related allergies. Most patients with food allergies induced by GRP show allergic symptoms accompanied by cofactors, such as exercise or drugs. To date, there are very few reports of generalized symptoms induced by strawberry. Case presentation We evaluated the reactivity of strawberry GRP in a 15-year-old boy who was confirmed to have generalized symptoms induced by strawberry with exercise using an oral food challenge test (OFCT). The patient’s serum exhibited a strong positive reaction to strawberry GRP but not to peach GRP or peach LTP. The patient’s basophils reacted to strawberry and peach GRP but not to peach LTP. Conclusions Strawberry GRP may be a causative component for strawberry with exercise-induced generalized symptoms in this patient. This is the first study to investigate the role of GRP in strawberry with cofactor-induced allergic symptoms. Further epidemiological and clinical researches are necessary to improve diagnostic and therapeutic approaches for patients with strawberry allergy.

Objectives: Fish roe is a common allergen in Japan. We have previously reported that although immunoglobulin (IgE) from patients with salmon roe (SR) or pollock roe (PR) allergies cross-react, 70% of patients with SR allergy can consume PR without developing any symptoms. However, a correlation between clinical cross-reactivity and serological cross-reactivity remains to be demonstrated. Methods: Serum samples were collected from 15 patients with SR allergy who had consumed cooked PR previously. Among these volunteers, four had experienced immediate symptoms after consuming cooked PR, while the others had exhibited no symptoms of PR allergy. A competitive enzyme-linked immunosorbent assay (ELISA) was performed to analyze the serological cross-reactivity with SR and PR. Immunoblotting inhibition assays were performed using serum samples that had been pre-incubated with SR or PR extracts. Results: In ELISAs, binding to SR was inhibited by >50% when the serum samples from patients with both SR and PR allergies were pre-incubated with PR extract (p=0.0256). In immunoblots, pre-incubation of serum samples with PR extract inhibited detection of the 16-kDa protein, which likely corresponds to the major SR allergen beta' component, significantly more for samples from patients with both SR and PR allergies (100%) than for samples from those with only an SR allergy (18.2%) (p=0.011). Conclusions: The superior competitive binding of the sera from patients with both SR and PR allergies to PR compared with that to SR may induce clinical cross-reactivity between SR and PR.

Background The prognosis of postoperative recurrence in patients with non‐small cell lung cancer (NSCLC) is poor. However, depending on the recurrence patterns and treatment options, some patients can achieve long‐term survival following recurrence. In this study, we investigated the clinicopathological characteristics of NSCLC patients with curable disease who developed postoperative recurrence. Methods This retrospective study enrolled 535 patients who had developed recurrence from among 1760 consecutive patients with NSCLC who underwent curative resection from 1990 to 2008. Post‐recurrence cure was defined as being cancer‐free for at least five years after treatment for recurrence in patients who had undergone radical local treatment or chemotherapy. The clinicopathological characteristics associated with post‐recurrence cure were analyzed. Results Among 535 patients who developed recurrence, 24 (4.5%) achieved post‐recurrence cure. The median post‐recurrence follow‐up duration was 151 (85–275) months for those who achieved post‐recurrence cure. The solitary recurrent lesions and local treatment for the initial recurrence site were significantly more for patients who could be cured after they developed recurrence. All patients with post‐recurrence cure received only radical local treatment for the recurrent lesions. Conclusions Some patients with solitary recurrent NSCLC lesions can be cured with only radical local treatment. Key points Significant findings of the study The post‐recurrence cure patients maintained a cancer‐free status for five years after treatment for recurrence without a second recurrence. All patients with post‐recurrence cure received only radical local treatment for recurrence and had significantly higher number of solitary recurrent lesions. What this study adds Some patients with solitary recurrent NSCLC lesions after resection can be cured with only radical local treatment.

Objectives: We conducted a multicenter study using the same questionnaire in 1999 and 2014 to investigate changes in the characteristics of patients with latex allergy. Methods: We mailed questionnaires on latex allergy to hospitals in Japan that were members of the Japanese Latex Allergy Society. Results: We compared the 25 responses received in 2014 and the 81 responses received in 1999. With regard to the age distribution, the number of patients with latex allergy in their 20s declined significantly from 1999 to 2014 (P=0.004). The largest proportion of latex allergy cases was observed among those aged

Five years have passed since the Japanese Pediatric Guideline for Food Allergy (JPGFA) was first revised in 2011 from its original version. As many scientific papers related to food allergy have been published during the last 5 years, the second major revision of the JPGFA was carried out in 2016. In this guideline, food allergies are generally classified into four clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type of food allergy (urticaria, anaphylaxis, etc.), and (4) special forms of immediate-type of food allergy such as food-dependent exercise-induced anaphylaxis and oral allergy syndrome (OAS). Much of this guideline covers the immediate-type of food allergy that is seen during childhood to adolescence. Infantile atopic dermatitis associated with food allergy type is especially important as the onset of most food allergies occurs during infancy. We have discussed the neonatal and infantile gastrointestinal allergy and special forms of immediate type food allergy types separately. Diagnostic procedures are highlighted, such as probability curves and component-resolved diagnosis, including the recent advancement utilizing antigen-specific IgE. The oral food challenge using a stepwise approach is recommended to avoid complete elimination of causative foods. Although oral immunotherapy (OIT) has not been approved as a routine treatment by nationwide insurance, we included a chapter for OIT, focusing on efficacy and problems. Prevention of food allergy is currently the focus of interest, and many changes were made based on recent evidence. Finally, the contraindication between adrenaline and antipsychotic drugs in Japan was discussed among related medical societies, and we reached an agreement that the use of adrenaline can be allowed based on the physician's discretion. In conclusion, this guideline encourages physicians to follow the principle to let patients consume causative foods in any way and as early as possible.

Abstract Introduction Immune response to cow's milk allergen (CMA) has been analyzed mostly using crude milk antigen or a mixture of various caseins. This study aimed to assess the changes in the immunological response against αS1‐casein during oral immunotherapy (OIT) and to investigate the mechanism of tolerance. Methods We have performed rush OIT to 39 patients with CMA and obtained the serum samples up to 3 years after OIT. Immunoglobulin E (IgE) and IgG4 antibodies specific to highly purified αS1‐casein as well as passively‐sensitized basophil activation were evaluated using the serial samples. Furthermore, we examined whether basophil activation led by the pre‐OIT serum was suppressed by the post‐OIT serum, or by the tolerant serum obtained from naturally outgrown patients. Results Specific IgE to αS1‐casein was significantly reduced after OIT. Specific IgG4 (sIgG4) to αS1‐casein was also detected in most of the pre‐OIT sera, which was not significantly increased after OIT. Activation of passively‐sensitized basophils to αS1‐casein was significantly reduced after 2 years (14% ± 19%) and 3 years (19% ± 18%) post‐OIT compared with pre‐OIT (%CD63high basophils; 51% ± 27%). Furthermore, the addition of post‐OIT or tolerant serum to pre‐OIT serum significantly suppressed the basophil activation. This suppression was abrogated by washing the supernatant after passive sensitization, but not by depleting IgG antibodies from post‐OIT or tolerant sera, nor by blocking FcγRIIb using an anti‐FcγR antibody. Conclusions αS1‐casein‐sIgG4 plays a minor role in tolerance mechanisms in cases of CMA; humoral factors other than antigen‐sIgG4 may be involved.

Infantile wheezing and eczema are associated with the subsequent onset of asthma and other atopic diseases. However, there are no large population-based surveys on infantile allergic symptoms in Japan. The objective of the study was to determine the prevalence of wheezing and asthma in infants in Nagoya, Japan. This population-based cross-sectional study was performed in the metropolitan city of Nagoya, Japan. We surveyed parents to ascertain the prevalence of wheezing and eczema in infants who attended group health checkups at 3, 18, and 36 months of age. Their parents completed modified questionnaires from the International Study of Asthma and Allergies in Childhood. More than 90% of the approximately 40,000 children in each study group living in the target area were included in the survey. The prevalence of wheezing was 8%, 17%, and 13% at 3, 18, and 36 months, respectively, and was characterized by birth season. The prevalence of eczema was 24%, 30%, and 31%, at 3, 18, and 36 months, respectively. Participants born in autumn and winter had a higher incidence of eczema in each age group. Three-quarters of the children had a parental history of allergic conditions. Parental allergic diseases and male gender are risk factors for wheezing and eczema in children. This survey had a high response rate and covered almost the entire population of the target age groups in a large city. We believe that the results of this study, therefore, provide a much higher level of confidence regarding the prevalence of allergies in infants in Japan than that in previous studies with limited cohorts.

Parvalbumins are small molecules with important functions in Ca2+ signaling, but their sequence comparisons to date, especially in fish, have been relatively poor. We here, characterize sequence motifs that distinguish parvalbumin subfamilies across vertebrate species, as well as those that distinguish individual parvalbumins (orthologues) in fish, and map them to known parvalbumin structures. As already observed by others, all classes of jawed vertebrates possess parvalbumins of both the α-parvalbumin and oncomodulin subfamilies. However, we could not find convincing phylogenetic support for the common habit of classifying all non-α-parvalbumins together as “β-parvalbumins.” In teleost (modern bony) fish, we here distinguish parvalbumins 1-to-10, of which the gene copy number can differ between species. The genes for α-parvalbumins (pvalb6 and pvalb7) and oncomodulins (pvalb8 and pvalb9) are well conserved between teleost species, but considerable variation is observed in their copy numbers of the non-α/non-oncomodulin genes pvalb1-to-5 and pvalb10. Teleost parvalbumins 1-to-4 are hardly distinguishable from each other and are highly expressed in muscle, and described allergens belong to this subfamily. However, in some fish species α-parvalbumin expression is also high in muscle. Pvalb5 and pvalb10 molecules form distinct lineages, the latter even predating the origin of teleosts, but have been lost in some teleost species. The present study aspires to be a frame of reference for future studies trying to compare different parvalbumins.

Background: Generally, oral immunotherapy (OIT) aims for daily administration. Recently, the efficacy of treatment with OIT at a low dose has been reported. However, the optimal dose and the evaluation of dose-dependent OIT outcome have not been described. Methods: A multicenter, parallel, open-labeled, prospective, non-placebo controlled, randomized study enrolled 101 Japanese patients for treatment with OIT. We hypothesized that target dose OIT would induce short-term unresponsiveness (StU) earlier than reduced dose OIT. StU was defined as no response to 6200 mg whole egg, 3400 mg milk, and 2600 mg wheat protein, as evaluated by oral food challenge after 2-week ingestion cessation. To compare the two doses of OIT efficacy, the maximum ingestion doses during the maintenance phase of OIT were divided into 100%-dose or 25%-dose groups against their target StU dose, respectively. A total of 51 patients were assigned to the 100%-dose group [hen's egg (HE) = 26, cow's milk (CM) = 13, wheat = 12] and 50 to the 25%-dose group (HE = 25, CM = 13, wheat = 12). Primary outcome was established by comparing StU at 1 year. Secondary outcome was StU at 2 years and established by comparing allergic symptoms and immunological changes. Results: The year 1 StU rates (%) for the 100%- and 25%-dose groups were 26.9 vs. 20.0 (HE), 7.7 vs. 15.4 (CM), and 50.0 vs. 16.7 (wheat), respectively. The year 2 StU rates were 30.8 vs. 36.0 (HE), 7.7 vs. 23.1 (CM), and 58.3 vs. 58.3 (wheat), respectively. There were no statistically significant differences in StU between years 1 and 2. The total allergic symptom rate in the 25%-dose group was lower than that in the 100%-dose group for egg, milk, and wheat. Antigen-specific IgE levels for egg-white, milk, and wheat decreased at 12 months. Conclusions: Reduced maintenance dose of egg OIT showed similar therapeutic efficacy to the target dose. However, we were not able to clearly demonstrate the efficacy, particularly for milk and wheat. Reducing the maintenance dose for eggs, milk, and wheat may effectively lower the symptoms associated with their consumption compared to the target OIT dose. Furthermore, aggressive reduction of the maintenance dose might be important for milk and wheat, compared to the 25%-dose OIT. Trial registration: UMIN000009373, Multicenter Oral Immunotherapy for Hen's Egg, Cow's Milk, and Wheat-Allergic Children at Outpatient Clinic.

Background: To evaluate the long-term safety of subcutaneous immunotherapy with TO-204, a standardized house dust mite (HDM) allergen extracts, we conducted a multicenter, open label clinical trial. Methods: Japanese patients aged 5–65 years were eligible for the study, if they had HDM-induced allergic rhinitis (AR), allergic bronchial asthma (BA), or both. TO-204 was administered in a dose titration scheme, and the maintenance dose was determined according to the predefined criteria. The treatment period was 52 weeks, and patients who were willing to continue the treatment received TO-204 beyond 52 weeks. This clinical trial is registered at the Japan Pharmaceutical Information Center (Japic CTI-121900). Results: Between July 2012 and May 2015, 44 patients (28 with AR and 16 with allergic BA) were enrolled into the study. All patients were included in the analysis. The duration of treatment ranged from 23 to 142 weeks and the median maintenance dose was 200 Japanese allergy units (JAU). Adverse events occurred in 22 patients (50%). The most common adverse event was local reactions related to the injection sites. Four patients experienced anaphylactic reactions when they were treated with the dose of 500 JAU. Two patients experienced anaphylactic shock with the doses of 1000 JAU at onset. These 6 patients could continue the study with dose reduction. Conclusions: Safety profile of TO-204 was acceptable in Japanese patients with HDM-induced AR or allergic BA. Higher doses should be administered carefully, because the risk of anaphylaxis increased at doses of 500 or 1000 JAU. Keywords: Allergen immunotherapy, Allergic bronchial asthma, Allergic rhinitis, Clinical trial, House dust mite

Anterior mediastinal teratomas are common and are generally characterized as slow growing tumors. Very few reports documenting rapidly growing tumors exist. Here, we describe a case of a mature teratoma showing rapid growth in 1 year treated with complete surgical resection. Keywords: Mediastinal tumor, Mature teratoma, Rapidly growing, Testicular epidermoid cyst, Familial Mediterranean fever

Objectives: Oral allergy syndrome (OAS) associated with citrus fruits has been previously reported. However, in Japan, although rare, citrus allergy is also associated with food-dependent exercise-induced anaphylaxis (FDEIA). This study was done to determine whether different allergens may be involved in these two responses, and to examine cross-reactivity between popular citrus fruits and local pollen allergens. Methods:Twelve patients were studied who had a history of OAS (8 cases) or FDEIA (4 cases), and had positive IgE antibody titers or tested positive with a skin prick test to citrus antigens. Serum immunodetection assays and immunoblot inhibition assays were performed with extracted Valencia orange (rCit s 2), selected antigens in white birch pollen (WBP) and orchard grass pollen (OGP). Results: Immunodetection assays demonstrated an allergen associated with OAS as the 14-kDa protein, Cit s 2. An as yet unidentified 54-kDa protein was demonstrated in FDEIA patients. Cross-reactivity between orange and pollen antigens was confirmed by the following results: 1) Significant correlations between serum specific IgE levels for orange and OGP, 2) Immunoblot inhibition with WBP and OGP pollen antigens against rCit s 2. In Immunoblot inhibition, WBP and OGP both pollen antigens inhibited against rCit s 2. Conclusion: The main allergen of OAS induced by orange was Cit s 2, which has cross-reactivity with WBP and/or OGP in Japanese patients with orange allergy. IgE-binding protein pattern in patients with FDEIA induced by orange were different from that in OAS. A 54-kDa protein was assumed to be a candidate for clinically relevant allergens in the development of the FDEIA.

Background: In recent years, it has been proposed that the primary mechanism for the development of food allergies is percutaneous sensitization. Since 2010, in Japan, the number of immediate-type wheat allergy due to hydrolyzed wheat protein has dramatically increased among those who have been using soap containing hydrolyzed wheat. This incidence supports the hypothesis that food allergens arise through percutaneous sensitization. Clinical Summary: A 25-year-old man (case 1) and an 18-year-old girl (case 2) with atopic dermatitis visited our Department because of food allergy and hand eczema. After starting their work with fish, severe itchy eczema appeared on their hands. They subsequently started to experience oral allergic symptoms, intraoral itchiness and dyspnea after eating fish. Specific IgE antibodies were detected for many fishes, and skin prick tests showed positive reactions for a variety of fishes in both cases. Furthermore, the fluorescence intensities of specific IgE antibodies against parvalbumin from various types of fish in microarray immunoassay analysis showed positive reactions. We diagnosed them as contact urticaria caused by percutaneous sensitization to parvalbumin through job-related physical contact with fish. Conclusion: The patients' histories and findings indicate the possibility of percutaneous sensitization through occupational exposure to parvalbumin, leading to food allergy.

Oral allergy syndrome (OAS) is defined as the symptoms of IgE-mediated immediate allergy localized in the oral mucosa, and the characteristics depend on the lability of the antigen. Another term used for this syndrome is pollen-food allergy (PFS); the patient is sensitized with pollen via the airways and exhibits an allergic reaction to food antigen with a structural similarity to the pollen (class 2 food allergy). In addition to PFS, latex-fruit syndrome is also well-known as the disease exhibiting OAS. In treating the condition, it must be noted that most but not all symptoms of PFS are those of OAS. In many cases, antigens become edible by heating, but some are resistant to heating. Also, since the exacerbation of atopic dermatitis is occasionally observed after the intake of cooked antigens in asymptomatic individuals, careful inquiry of the history is important in designing the treatment. Immunotherapy against the cross-reacting pollen has also been attempted in PFS.

Background: Salmon is one of the most widely consumed seafoods in Japan and many other countries around the world. Due to the confirmed cases of salmon-induced allergy, the food sanitation law in Japan stipulates salmon as one of the specific food items for which labeling is recommended when used as an ingredient of processed foods. However, trout, the landlocked form of anadromous salmon, is not subject to the allergenlabeling requirements, even though both populations belong to a single species. Since no supporting data have been demonstrated to make a clear distinction between these two populations in terms of allergenicity, we comparatively examined their allergenic properties using sera from patients allergic to fish. Methods: Extracts of Oncorhynchus nerka from different habitats were obtained: kokanee (landlocked) and red salmon (anadromous). Control extracts were derived from four other species. This study focused on the (1) IgE-binding capacity of the fish extracts in patients' sera (n=50), (2) ELISA inhibition test (n=6), and (3) inhibition immunoblot test (n=8) between the kokanee and red salmon. Results: The extracts from kokanee and red salmon showed the highest correlation with each other in terms of the IgE-binding capacity, and showed complete (100%) reciprocal cross-inhibition in the ELISA inhibition test. On immunoblotting, there was no marked difference in the staining pattern between the two extracts, and each IgE-binding band gradually disappeared when the patients' sera were preincubated with the counterpart antigen in a dose-dependent manner. Conclusions: These results suggest that kokanee has similar allergenic properties to red salmon.

Background: Hypersensitivity reactions to fish are a common food allergy, but IgE-binding activity to fish species have not been fully elucidated. The aim of this study was to identify fish with high binding activity to IgE in sera from Japanese fish-hypersensitive individuals. Methods: 38 children with a history of at least one episode of hypersensitivity after ingestion of fish were enrolled and 34 children with no history of reactions and negative IgE results for at least five kinds of fish antigen were included as controls. Using a radioallergosorbent test, we examined IgE-binding to each fish species using sera from fish-hypersensitive subjects. Fish were then graded according to IgE-binding activity. Results: Many fish species, including red salmon, silver salmon, yellowfin tuna, big eyed tuna, Atlantic tuna, saurel, skipper, yellowtail, Japanese sardine, bonita and mackerel had high IgE-binding activity. All of these fish are abundantly consumed in Japan. The hypersensitivity reactions experienced by many subjects occurred after ingestion of species with high IgE-binding activity. Only halibut (Osteichthyes) and sharks (Chondrichthyes) had low IgE-binding activity. Conclusions: A correlation was observed between IgE levels and expression of symptoms after fish ingestion. High consumption of salmon, tuna, scad (including saurel), skipper, yellowtail, sardine, bonita and mackerel in Japan might be the cause of the high IgE-binding activity of these species. The grades of fish species consumed widely in Japan are likely to be useful for nutritional instruction of fish-allergic patients.