Summer-type Hypersensitivity Pneumonitis Research Articles

Effect of warm and humid days on the positivity rate of anti-Trichosporon asahii antibody test for the diagnosis of summer-type hypersensitivity pneumonitis

BackgroundSummer-type hypersensitivity pneumonitis (SHP) has been reported to occur during warm and humid summer seasons in Japan; however, the effect of weather conditions on SHP remains unknown. Anti-Trichosporon asahii antibody (TaAb) test is highly specific and useful for the diagnosing SHP. Therefore, we aimed to investigate the impact of weather conditions on SHP by examining the relationship between the positivity rate of TaAb and warm and humid days. MethodsTaAb test data from June 2013 to June 2020 were obtained from major commercial laboratories to determine the number of samples and positivity rate of TaAb by prefecture. Using the Japan Meteorological Agency database, we counted the warm and humid days (maximum temperature ≥25 °C and average humidity ≥80 %) for each prefecture. Negative binomial regression was employed to examine the relationship between the positivity rate of TaAb and the number of warm and humid days per month. ResultsA total of 79,211 samples and 7626 positive samples (9.6 %) were identified. We found that the number of warm and humid days, 1 or 2 months prior to testing for TaAb, was associated with the positivity rate of the test. An increase in the positivity rate by 1.6 % and 2.9 % was observed with every 1-day increase in warm and humid days 1 month and 2 months before the test, respectively. ConclusionsOur TaAb analysis revealed a significant increase in TaAb positivity 1 or 2 months after periods of warm and humid days.

Database analysis of hypersensitivity pneumonitis in Japan

BackgroundThree epidemiological small-scale studies on hypersensitivity pneumonitis (HP) have been performed in Japan to date. Herein, we aimed to clarify the clinical characteristics of various types of HP diseases using a large nationwide database in Japan. MethodsWe used the Japanese Diagnostic Procedure Combination database that includes data from 1,031 participant hospitals. Patients with HP from 2011 to 2017 were identified using International Classification of Diseases 10th Revision codes. We analyzed patient characteristics, the yearly transition of the number of HP cases, rate per one million hospitalizations, geographical distribution, seasonality, and risk factors for in-hospital mortality. ResultsIn total, 3,634 patients with HP were identified, including summer-type HP (SHP) (n = 490), bird fancier's lung (BFL) (n = 199), ventilation pneumonitis (n = 106), farmer's lung (n = 48), and unspecified HP (n = 2761). The length of hospital stay was significantly longer in patients with BFL (19 days) than in patients with SHP (15 days). SHP was more prevalent in the southwestern region of Japan, and hospitalization occurred mainly in summer (37.8%) and fall (37.3%). Ventilation pneumonitis was predominant in winter (28.6%) and spring (38.7%). In-hospital mortality was significantly associated with old age (p < 0.001), low body mass index (p = 0.016), severe dyspnea (p < 0.001), and BFL diagnosis on admission (p = 0.031). ConclusionsThis study revealed the clinical characteristics of SHP and BFL, including the frequency of causative antigens, geographical distribution, seasonality, and risk factors for mortality, which may help in diagnosing HP and identifying causative antigens.

Winter-onset Summer-type Hypersensitivity Pneumonitis Related to a Warm Climate: A Case Report and Review of the Literature

Winter-onset Summer-type Hypersensitivity Pneumonitis Related to a Warm Climate: A Case Report and Review of the Literature

Features of humidifier lung and comparison with summer‐type hypersensitivity pneumonitis

Humidifier lung is a phenotype of hypersensitivity pneumonitis (HP) caused by the inhalation of humidifier vapours. A recent study comparing humidifier lung with summer-type HP reported several distinct features, including lower serum Krebs von den Lungen-6 (KL-6) levels, less common centrilobular ground-glass nodules on computed tomography scan and a higher ratio of CD4+ to CD8+ cells in bronchoalveolar lavage.1 However, the features and mechanisms of humidifier lung are not well characterized. Indicators for discrimination of humidifier lung from other phenotypes of HP are uncertain. Here, we report more characteristics of histopathological findings and a diagnostic predictor for humidifier lung compared to summer-type HP, which is the most common phenotype of HP in Japan.1, 2 Among 82 adult patients hospitalized for HP at Fukujuji Hospital from April 1999 to March 2018, 7 patients with humidifier lung (18.3%) and 26 patients with summer-type HP (43.3%) were enrolled, 22 patients with unfulfilled diagnostic criteria of HP3 and 27 patients with other phenotypes of HP were excluded (15 patients with various exposures to fungi contaminating a house, 4 patients with bird fancier's lung and 8 patients with unknown origin). The diagnosis of HP was based on criteria outlined in the official American Thoracic Society, Japanese Respiratory Society and Asociación Latinoamericana del Tórax (ATS/JRS/ALAT) clinical practice guideline 2020.3 The baseline characteristics of the patients are shown in Table 1. The humidifier lung group showed faster disease progression (shorter duration from symptom onset to hospital visit) than the summer-type HP group (median (interquartile range (IQR)): 6.0 (3.0–17.5) vs 30.0 days (17.8–57.5), P = 0.006). Granulomas in histopathological findings were significantly less common in humidifier lung patients than in summer-type HP patients (n = 0 (0.0%) vs n = 9 (56.3%), P = 0.045). Serum KL-6 levels were significantly lower in humidifier lung patients than in summer-type HP patients (median (IQR): 316 (303–587 U/mL) vs 1690 U/mL (1093–3385 U/mL), P < 0.001). The area under the receiver operating characteristic curve for serum KL-6 for distinguishing humidifier lungs from summer-type HP was 0.887. When the cut-off value of serum KL-6 was less than 674 U/mL, the sensitivity, specificity and odds ratio (OR) were 85.7%, 95.7% and 83.4 (95% CI: 5.3–5909.3), respectively. Generally, the mechanism of HP other than humidifier lung is extrinsic allergic alveolitis with type III (immune complex-mediated) or IV (delayed) granulomas.4 However, antigens associated with humidifier lung have been reported in patients exposed to not only various bacteria and fungi but also endotoxins.4, 5 The mechanism of humidifier lung might be different from the other phenotypes of HP because of less frequent granuloma formation, faster disease progression and lower KL-6 levels, as we have shown. We believe that one of the different mechanisms is related to exposure to endotoxins; however, there is no report demonstrating the presence of endotoxins in humidifier vapours. Therefore, examination of both humidifier water and vapours is warranted in future. clinical allergy and immunology, environmental & occupational health and epidemiology, interstitial lung disease, rare lung disease. Conceptualization: M.S. Data curation: M.S., Y.T., K.F., T.O., R.Y., H.K. Formal analysis: M.S. Investigation: M.S. Methodology: M.S., K.M., Y.T. Project administration: M.S., K.M., K.Y., K.O. Software: M.S. Supervision: K.M., K.Y., K.O. Validation: M.S. Visualization: M.S. Writing—original draft: M.S., K.M. Writing—review and editing: M.S., K.M., K.O.

Summer-type hypersensitivity pneumonitis in a share house for foreigners in Japan.

Summer-type hypersensitivity pneumonitis commonly occurs in Japan during the warm and humid season, when the causative Trichosporon asahii flourish. The assessment of anti-T. asahii antibodies in patients with hypersensitivity pneumonitis without any obvious causative antigen may be useful even outside Japan.

Clinical and radiological characteristics of ultrasonic humidifier lung and summer-type hypersensitivity pneumonitis

BackgroundUltrasonic humidifier lung is a rare form of hypersensitivity pneumonitis (HP), and its clinical and radiological features are unclear. This study examined the clinical and radiological characteristics of humidifier lung. MethodsData from 18 patients with humidifier lung (mean age, 67.3 years) diagnosed during October 2012 through April 2018 were retrospectively reviewed. We compared clinical, laboratory, and CT findings and bronchoalveolar lavage fluid (BALF) characteristics of these patients with those of 19 patients with summer-type HP (mean age, 57.4 years). ResultsCough and dyspnea were the most common symptoms. White blood cell count and serum C-reactive protein titers were higher for humidifier lung than for summer-type HP. Serum levels of Krebs von den Lungen-6 and surfactant protein D were significantly lower for humidifier lung than for summer-type HP. The most common chest CT findings in humidifier lung were ground-glass opacities (88.9%) and mosaic attenuation (50.0%). Centrilobular ground glass nodules were less common in humidifier lung than in summer-type HP (27.8% vs 63.1%; P = 0.043). Peribronchovascular or subpleural nonsegmental consolidation was more frequent in humidifier lung than in summer-type HP (44.4% vs 5.3%; P = 0.013). Lymphocyte fractions in BALF specimens were significantly lower for humidifier lung than for summer-type HP (37.3% vs 69.0%; P < 0.001). Neutrophil fractions were higher for humidifier lung, but the difference was not significant (22.1% vs 8.1%; P = 0.153). The CD4/8 ratio was higher for humidifier lung than for summer-type HP (1.7 vs 0.8; P = 0.003). ConclusionsThe clinical and radiological characteristics of humidifier lung differ from those of summer-type HP.

居住環境に起因する健康障害−古い住宅で発症した夏型過敏性肺炎の 2 事例

居住環境に起因する健康障害−古い住宅で発症した夏型過敏性肺炎の 2 事例

Clinical features of chronic summer-type hypersensitivity pneumonitis and proposition of diagnostic criteria.

Trichosporon asahii (T. asahii) causes chronic summer-type hypersensitivity pneumonitis (C-SHP); however, little is known about the clinical features of this condition. We aimed to elucidate the clinical features of C-SHP and propose practical diagnostic criteria for C-SHP based on the presence of serum anti-T. asahii antibody (TaAb). Patients diagnosed with C-SHP and idiopathic pulmonary fibrosis (IPF) between January 2010 and May 2017 were reviewed retrospectively. Clinical findings were compared between the two groups. Criteria for C-SHP were proposed on the basis of significant characteristics and applied to the development and validation cohorts. Thirty-one patients with C-SHP and 26 with TaAb-negative IPF were identified. C-SHP patients were more likely to live in wooden houses; their serum Krebs von den Lungen-6 (KL-6) and serum surfactant protein-D (SP-D) levels were higher than those of IPF patients. C-SHP patients were more likely to have subpleural consolidation, micronodules, and extensive ground-glass opacification on high-resolution computed tomography (HRCT). The following 3 items were considered to have diagnostic value: I) TaAb positivity; II) an HRCT pattern consistent with chronic hypersensitivity pneumonitis, including mosaic attenuation or micronodules; and III) elevated serum biomarker levels (KL-6>1500 U/mL or SP-D>250ng/mL). We defined cases satisfying I) and II) as "probable C-SHP" and those satisfying all 3 criteria as "confident clinical diagnosis of C-SHP". The areas under the receiver-operating curve were 0.965 and 0.993 in the development and validation cohorts, respectively, which suggested that these criteria had good discriminative ability in clinical evaluations. Clinical features could be useful for distinguishing C-SHP from IPF and other etiologies of ILDs.

A CASE OF SUMMER-TYPE HYPERSENSITIVITY PNEUMONITIS ACCOMPANIED BY THE SYNDROME OF INAPPROPRIATE SECRETION OF ANTIDIURETIC HORMONE

A 47-year old man presented to our hospital with a 6-month history of malaise, cough and dyspnea on exertion. Laboratory testing revealed the severe hyponatremia. A chest X-ray showed bilateral diffuse micronodules. Anti-Trichosporon asahii antibody and environmental provocation test were positive. Bronchoalveolar lavage fluid showed lymphocytosis and low CD4/8 ratio. The specimens obtained by transbronchial lung biopsy revealed alveolitis. Based on these findings, the patient was diagnosed as having summer-type hypersensitivity pneumonitis (SHP). The patient was treated with antigen avoidance and oral corticosteroid. The hyponatremia caused by syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was treated with normal saline and water restriction. Serum sodium level was improved with treatment of SHP, which suggested the relevance between SHP and SIADH.

Protein antigen of bird-related hypersensitivity pneumonitis in pigeon serum and dropping

BackgroundAvian antigen is a common cause of hypersensitivity pneumonitis (HP). Inhalation challenge with pigeon serum and pigeon dropping extract (PDE) elicits a hypersensitivity reaction in patients with bird-related hypersensitivity pneumonitis (BRHP), but the antigenic components in these materials have yet to be fully elucidated.MethodPigeon serum, pigeon intestine homogenates, and PDE were immunoblotted with serum samples from 8 patients with BRHP, 2 patients with summer-type HP, 2 patients with humidifier lung, and 3 healthy volunteers. Among the protein spots found in both pigeon serum and PDE, those that reacted with sera from BRHP patients were identified by mass spectrometry. Immunoassays using recombinant protein were performed to confirm the antigenicity of the identified protein. Cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with recombinant protein was also assessed.ResultsImmunoglobulin lambda-like polypeptide-1 (IGLL-1) was identified from all spots on 2-DE immunoblots of both pigeon serum and PDE. The BRHP patients exhibited higher levels of serum IgG antibody against the recombinant IGLL-1 (rIGLL-1) compared to the control subjects, as well as a stronger PBMCs proliferative response to rIGLL-1. Cytokine production by PBMCs from BRHP patients after rIGLL-1 exposure indicated that the protein could induce Th1 prone immune responses: an increase in TNF-α and an absence of elevated IL-10 production.ConclusionsPigeon IGLL-1 was identified as the BRHP antigen present in both pigeon serum and PDE.

The Relationship between the Incidence of Summer-type Hypersensitivity Pneumonitis and Environmental Factors in Southern Tochigi Prefecture.

Objective Environmental and climatic changes have been occurring throughout the past 20 years in Japan. Correspondingly, the antigens that cause hypersensitivity pneumonitis might be changing. In an epidemiological survey of Japan in the 1980s, summer-type hypersensitivity pneumonitis (SHP) accounted for 74.4% of the cases of hypersensitivity pneumonitis. The epidemiological characteristics of this disease have not been reported since then. We investigated the annual changes in the number of cases of SHP and the factors affecting the results. Methods Cases that were diagnosed as SHP were retrieved from the medical records of our institute between 1990 and 2015. The diagnostic criteria proposed by the Japanese Ministry of Health, Labour and Welfare in 1990 were applied to obtain the definite diagnosis. Patients The study population included 25 diagnosed patients, including one intrafamilial case. The subjects were predominantly non-smoking women in their 50s and all lived in wooden houses that had been constructed more than 10 years previously. Results The number of cases that were diagnosed as SHP tended to decrease during the study period. However, temporal increases tended to occur in years with increased rainfall and decreased daylight hours. No relationship appeared to exist between the number of cases and high temperatures or humidity levels. Conclusion The incidence of SHP currently appears to be decreasing; however, the weather conditions in any given year might cause a temporal increase in the incidence rate.

リンフォカインの立場から : 夏型過敏性肺臓炎患者の血清並びに BAL 液中の可溶性インターロイキン 2 受容体の測定とその意義(2. 病態生理学的意義, BALF で何がわかるか)

リンフォカインの立場から : 夏型過敏性肺臓炎患者の血清並びに BAL 液中の可溶性インターロイキン 2 受容体の測定とその意義(2. 病態生理学的意義, BALF で何がわかるか)

Draft Genome Sequence of the Causative Antigen of Summer-Type Hypersensitivity Pneumonitis, Trichosporon domesticum JCM 9580.

Here, we report the draft genome sequence of Trichosporon domesticum JCM 9580, isolated from the house of a patient with summer-type hypersensitivity pneumonitis (SHP) in Japan. This genomic information will help elucidate the mechanisms of the development of SHP.

A critical role of Dectin-1 in hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a pulmonary disease caused by repeated exposure to various aspiration antigens, including bacteria and fungi. Although TLRs are known to be required for the generation of HP triggered by bacteria, the significance of fungal receptors remains unclear. The present study aimed to investigate whether Dectin-1 and Dectin-2 contribute to the development of experimental HP triggered by the fungus Trichosporon asahii (T. asahii) that causes summer-type HP. We investigated the binding between Dectin-Fc protein and T. asahii by a dot blot assay. We performed the histological and flow cytometric analysis in the HP model using Dectin-1-deficient (Dectin-1(-/-)) and Dectin-2(-/-) mice. We also investigated Th17/Th1 responses in lung cells, and measured an IL-17-promoting cytokine IL-23 from bone marrow-derived dendritic cells (BMDCs) by ELISA. Dectin-1 bound more strongly to T. asahii than Dectin-2. Dectin-1(-/-) mice barely developed HP, whereas both wild-type mice and Dectin-2(-/-) mice developed similar lung diseases. Dectin-1 deficiency decreased the infiltration of neutrophils and monocyte-derived macrophages and repressed the expansion of lung CD4(+)IL-17A(+) cells. The production of IL-23 p19 was reduced in Dectin-1(-/-) BMDCs. These data suggested Dectin-1 plays a critical role in the development of fungus-induced HP.

Utility of immunological tests for bird-related hypersensitivity pneumonitis.

The reaction of specific antibodies and sensitized lymphocytes to antigens is important in hypersensitivity pneumonitis (HP). However, there are no known studies evaluating the utility of the lymphocyte proliferation test (LPT) or specific antibodies to avian antigens in diagnosing bird-related HP. In this study, we examined the sensitivity and specificity of these two tests. Patients with acute bird-related HP (n=10), chronic bird-related HP (n=35), acute summer-type HP (n=14), and other interstitial pneumonia (IP) (n=76) were evaluated. The optimal cutoff values were determined by receiver operating curve (ROC) analyses of specific antibodies in serum and bronchoalveolar lavage fluid (BALF), and by conducting the LPT on mononuclear cells in peripheral blood and BALF. The sensitivity and specificity of the antibodies were 80-100% and 92-100% in acute bird-related HP, and 26-79% and 73-93% in chronic bird-related HP, respectively. The sensitivity and specificity of the LPT were 50-100% and 100% in acute bird-related HP, and 46% and 91% in chronic bird-related HP, respectively. Specific antibodies and the LPT are quite useful for diagnosing acute bird-related HP. The presence of specific antibodies in BALF and the results of LPT with peripheral blood mononuclear cells are particularly useful for diagnosing chronic bird-related HP.

Differentiation of the Emerging Human Pathogens Trichosporon asahii and Trichosporon asteroides from Other Pathogenic Yeasts and Moulds by Using Species-Specific Monoclonal Antibodies

The fungal genus Trichosporon contains emerging opportunistic pathogens of humans, and is the third most commonly isolated non-candidal yeast from humans. Trichosporon asahii and T. asteroides are the most important species causing disseminated disease in immunocompromised patients, while inhalation of T. asahii spores is the most important cause of summer-type hypersensitivity pneumonitis in healthy individuals. Trichosporonosis is misdiagnosed as candidiasis or cryptococcosis due to a lack of awareness and the ambiguity of diagnostic tests for these pathogens. In this study, hybridoma technology was used to produce two murine monoclonal antibodies (MAbs), CA7 and TH1, for detection and differentiation of Trichosporon from other human pathogenic yeasts and moulds. The MAbs react with extracellular antigens from T. asahii and T. asteroides, but do not recognise other related Trichosporon spp., or unrelated pathogenic yeasts and moulds including Candida, Cryptococcus, Aspergillus, Fusarium, and Scedosporium spp., or the etiologic agents of mucormycosis. Immunofluorescence and Western blotting studies show that MAb CA7, an immunoglobulin G1 (IgG1), binds to a major 60 kDa glycoprotein antigen produced on the surface of hyphae, while TH1, an immunoglobulin M (IgM), binds to an antigen produced on the surface of conidia. The MAbs were used in combination with a standard mycological growth medium (Sabouraud Dextrose Agar) to develop an enzyme-linked immunosorbent assay (ELISA) for differentiation of T. asahii from Candida albicans and Cryptococcus neoformans in single and mixed species cultures. The MAbs represent a major advance in the identification of T. asahii and T. asteroides using standard mycological identification methods.

Familial summer-type hypersensitivity pneumonitis in Japan: two case reports and review of the literature

BackgroundHypersensitivity pneumonitis is defined as an allergic lung disease that occurs in response to inhalation of fungal antigens, bacterial antigens, chemicals, dusts, or animal proteins. The incidence of summer-type hypersensitivity pneumonitis is higher in the summer season, especially in Japan, due to the influence of the hot and humid environment and the common style of wood house or old concrete condominiums.Case presentationThe present report describes a case of a middle-aged married couple who lived in the same house and who simultaneously suffered from summer-type hypersensitivity pneumonitis. This report analyzes these two cases in terms of environmental research and its microbiological, radiological, and pathological aspects. This case report is followed by a review of family occurrences of summer-type hypersensitivity pneumonitis from 22 studies with a total of 49 patients (including the two present cases) in Japan.ConclusionSummer-type hypersensitivity pneumonitis may be unrecognized and misdiagnosed as pneumonia or other respiratory diseases. A greater understanding of the clinical, pathologic, and environmental features of summer-type hypersensitivity pneumonitis might help improve diagnosis and delivery of appropriate management for this condition.

A nationwide epidemiological survey of chronic hypersensitivity pneumonitis in Japan

In 1999, a Japanese epidemiological survey of chronic hypersensitivity pneumonitis (HP) showed that summer-type HP was the most prevalent variant of the disease. The number of reported cases of chronic HP has recently been increasing, and the clinical features of the disease seem to have changed. We conducted another nationwide epidemiological survey of chronic HP in Japan to determine better estimates of the frequency and clinical features of the disease. A questionnaire was sent to qualified hospitals throughout Japan, and data on cases of chronic HP diagnosed between 2000 and 2009 were collected. In total, 222 cases of chronic HP from 22 hospitals were studied. Disease subtypes included bird-related HP (n=134), summer-type HP (n=33), home-related HP (n=25), farmer's lung (n=4), isocyanate-induced HP (n=3), and other types (n=23). The median proportion of lymphocytes in bronchoalveolar lavage fluid was high (24.5%). The primary findings of computed tomography of the chest were ground-glass attenuation and interlobular septal thickening. Centrilobular fibrosis was the major pathological finding on examination of surgical lung biopsy specimens from 93 patients. The median survival time was 83 months. The proportion of bird-related HP was higher than that in the previous epidemiological survey, and the proportions of isocyanate-induced HP and farmer's lung were lower. A crucial step in diagnosing chronic HP is to thoroughly explore the possibility of antigen exposure.

Pathogenesis of summer-type hypersensitivity pneumonitis

Summer-type hypersensitivity pneumonitis (SHP) is the most prevalent type of HP in Japan, and the major causative agent of the disease is T. cutaneum. The major antigenic substance of the yeast is serotype-related polysaccharide. Home environmental factors indicate that SHP is a sick house syndrome. Immunologically, both humoral and cellular hypersensitivities are involved in the induction of the disease. The levels of specific IgG and IgA antibodies and complements in BAL fluids from SHP patients are well correlated to the clinical course. On the other hand, BAL lymphocytes in SHP patients are mostly T lymphocytes, mainly due to an increase in CD8+ subpopulations of lymphocytes; this leads to a decrease in the ratio of CD4+ to CD8+. These T cells belong to CD45RO+ memory T lymphocytes and LFA-11 alpha high+ cytotoxic T lymphocytes as assessed by their cell surface phenotypes. However, functions of these BAL T lymphocytes remain undefined. Host factors such as HLA-DQw3 and cigarette smoking may participate in the development of the disease. In conclusion, the pathogenesis of SHP is considered to be a combination of immune complex disease and cellular hypersensitivity to T. cutaneum.

Specific antibody-forming cells in bronchoalveolar lavage fluid of patients with summer-type hypersensitivity pneumonitis--detection by enzyme-linked immunospot (ELISPOT)

Antigen-specific antibody-forming cells (AFCs) were assessed in bronchoalveolar lavage (BAL) fluid of patients with summer-type hypersensitivity pneumonitis by the method of enzyme-linked immunospot (ELISPOT). Both Cryptococcus- and Trichosporon-specific AFCs of isotypes of IgG, IgA and IgM were detected in BAL fluid cells. The frequency of isotypes of AFCs was in the order of IgA > IgM > IgG. Antibody activities against both Cryptococcus and Trichosporon antigens were detected in the culture supernatant of BAL cells. A good correlation was observed between the number of AFCs and the degree of antibody activity of culture supernatant of BAL cells, particularly of IgA isotype. For the IgM and IgA isotypes, anti-Cryptococcus antibody activity correlated well with anti-Trichosporon antibody activity (r = 0.98, p < 0.0001). In several cases examined, antigen-specific AFCs were detected in in vitro culture of peripheral blood mononuclear cells of patients after stimulation with PWM. In the present study, we demonstrated that Cryptococcus neoformans and Trichosporon cutaneum antigen-specific AFCs were present in the lungs of patients with summer-type hypersensitivity pneumonitis, and the antibodies secreted therefrom reacted with both these antigens. The presence of memory B cells was also suggested in the peripheral blood of patients.