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Adenomyosis is frequently observed in premenopausal women, and oral dienogest is the recommended treatment to target the underlying pathology and improve the symptoms. This retrospective study investigated the association of Lewis (b) antigen expression with outcomes of dienogest therapy among women with adenomyosis. Records from a total of 342 adenomyosis patients were analysed, who were prescribed with oral dienogest for a maximum of 16 weeks. Expression levels of Lewis (b) antigen were measured to categorize all patients into either Le (b)- and Le(b)+ groups. Treatment outcomes, in terms of uterine volume, menstrual flow, pain symptoms and quality of life, were compared between the two groups. While oral dienogest therapy showed considerable clinical efficacy in both groups of patients, the extent of improvements in treatment outcomes was significantly more pronounced in Le (b)- group than Le (b)+ group, with respect to treatment time, uterine symptoms, menstrual flow, pain symptoms and quality of life. No difference in adverse effects was observed between the two groups. Expression of Lewis (b) blood group antigen interferes with oral dialogist therapy among women with adenomyosis., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interests., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The Histo-blood group antigens (HBGA) are host genetic factors associated with susceptibility to rotavirus (RV) and human norovirus (HuNoV), the major etiological agents of viral acute gastroenteritis (AGE) worldwide. The FUT2 gene expressing the alpha-1, 2-L- fucosyltransferase enzyme is important for gut HBGA expression, and also provides a composition of the phenotypic profile achieved through mutations occurring in populations with different evolutionary histories; as such, it can be considered a genetic population marker. In this study, Lewis and secretor HBGA phenotyping was performed using 352 saliva samples collected from children between three months and five years old born in the Amazon (Brazil, Venezuela and English Guyana) presenting AGE or acute respiratory infection (ARI), the latter considered as control samples. The total of children phenotyped as secretors was 323, corresponding to 91.80%. From these, 207 (58.80%) had a Le (a + b+) profile. The HBGA profiles were equally found in children with AGE as well as with ARI. The rs1047781 of the FUT2 gene was not detected in DNA from saliva cells with a Le (a+b+) profile. However, mutations not yet described in the FUT2 gene were observed: missense 325A>T, 501C>T, 585C>T, 855A>T and missense substitutions 327C>T [S (Ser) > C (Cys)], 446 T>C [L(Leu) > P(Pro)], 723C>A [N(Asn) > K(Lys)], 724A>T [I(Ile) > F(Phe)], 736C>A [H(His) > N(Asn)]. The SNP distribution in the FUT2 gene of the analyzed samples was very similar to that described in Asian populations, including indigenous tribes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The interaction between the ABO, FUT2 and FUT3 genes results in the synthesis of different glycoconjugates profiles expressed in gastrointestinal tract. Moreover, the protozoan Toxoplasma gondii, which causes toxoplasmosis, utilizes this organ as an infection route. We analyzed the frequencies of the different glycoconjugate profiles which were determined by phenotyping ABO and genotyping the status secretor (FUT2; substitution G428A) and Lewis (FUT3; substitution T202C and C314T) histo-blood systems, assessed by PCR-RFLP and PCR-SSP, respectively. A total of 244 pregnant women (G1: Seropositive; G2: Seronegative) for IgG T. gondii antibodies were enrolled. IgG anti-T. gondii antibodies were determined by ELISA. G1 was composed of 158 (64.8%) sample and G2 by 86 (36.2%). The glycoconjugate profile was accessed in 151 seropositive and 85 seronegative samples by the combination of ABO and Lewis phenotyping as well as FUT2 and FUT3 genotyping. In G1, 36 (22.8%) presented the glycoconjugate profile ALe b , 5 (3.3%) A, 13 (8.6) BLe b , 1 (0.6%) B, 41 (27.1%) Le b , 13(8.6%) H, 38(25.2%) Le a and 4 (2.6%) Le c . G2 was composed of 13 (15.3%) of ALe b , 15 (17.6%) BLe b , 1 (1.2%) B, 42 (49,4%) Le b and 14 (16.5) Le a . H and Le c glycoconjugate profiles were not found in G2. The frequencies of the glycoconjugates profiles Le b (p = 0.001) and H (p = 0.005) were significantly different compared between G1 and G2. The glycoconjugate profile H inferred from the ABO phenotyping and FUT3 and FUT2 genotyping is associated with infection by T. gondii in pregnant women and the Le b profile appears to protect the infection by this parasite., (Copyright © 2019. Published by Elsevier B.V.)

Background: Lewis serologic reagents frequently give inaccurate phenotyping results. Furthermore these serologic reagents are often used in nonserologic assays such as inhibition and immunohistochemistry. In both scenarios knowledge of the fine specificity and cross-reactivity of these reagents will improve the quality of results obtained., Study Design and Methods: A range of contemporary and historical workshop and developmental Lewis reagents including mouse monoclonal (MoAb) and human and goat polyclonal (PoAb) reagents were evaluated. All were evaluated both against Lewis kodecytes expressing only single Le(a) , Le(b) , ALe(b) , BLe(b) , Le(x) , Le(y) , ALe(y) , or BLe(y) antigens and against the same antigens inkjet printed on a paper-based microplate and analyzed by enzyme immunoassay. Nine clinical samples were also evaluated. A kodecyte antigen dilution sensitivity assay was used to establish the ratio of Le(b) antigen between group A1 /A2 and O RBCs., Results: A continuum of cross-reactivity from Le(x) through to H was observed with MoAbs. All PoAb and few MoAb anti-Le(a) samples and reagents cross-reacted to some degree with Le(b) antigen. Some PoAb and MoAb anti-Le(b) did not cross-react with Le(a) . All polyclonal goat anti-Le(b) reagents showed substantial activity against ALe(b) and BLe(b) , while no MoAb reagent had this activity. A1 RBCs had less than half the Le(b) antigen of A2 /O RBCs., Conclusions: Substantial cross-reactivity of both MoAbs and PoAbs with related antigens highlights the risks of using serologic reagents in nonserologic assays or against synthetic antigens. The lack of ALe(b) activity in anti-Le(b) MoAbs explains their poor performance against blood group A1 Le(a-b+) phenotypes., (© 2015 AABB.)

Background: Non-secretor individuals lack ABO blood group antigens in their secretions like saliva; these carbohydrate structures play an important role in protection of the oral cavity from exogenous pathogens; therefore these individuals are more susceptible to mucous membrane damages. The aim was to assess the secretory state of patients with oral lichen planus (OLP) in comparison with healthy controls., Methods: Fifty patients and 100 age-gender matched control subjects were recruited to the study. Patients were visited in the outpatient clinic of dermatology at Shohada-e-Tajrish Hospital, Shahid Beheshti University of Medical Sciences from 2012 - 2014. Two-milliliter (mL) blood was collected from each subject to detect Lewis phenotypes. According to Lewis phenotype of each subject, secretory state was determined except in subjects with Le (a-b-) phenotype, in whom saliva was collected to determine the secretor status., Results: Non-secretor status in patients with OLP was more frequent compared with healthy controls (37 out of 50 patients (74%) vs. 24 out of 100 healthy controls (24%), (P < 0.001)). There was no association between secretory state, and type of OLP and disease duration (P > 0.05)., Conclusion: This study supported the possible role of cell surface histo-blood group antigens in protection of mucosal surface from exogenous pathogens. Therefore, it appears that non-secretor individuals are more prone to oral lichen planus.

Background: Anti-Le(b) is usually a clinically insignificant antibody of immunoglobulin M subclass most often found in the sera of pregnant women or individuals that are Le(a-b-). We report a case of an acute hemolytic transfusion reaction due to a hemolytic anti-Le(b) that was not seen in the pretransfusion antibody detection test, but was strongly reactive in posttransfusion testing., Case Report: A 30-year-old African-American woman with metastatic renal cell carcinoma was receiving chemotherapy. She was anemic with hemoglobin (Hb) of 7.2 g/dL and had a negative antibody detection test by the solid-phase red blood cell adherence method. She was transfused with 2 RBC units without incident. Nine days later her Hb was 7.9 g/dL again with a negative antibody detection test. Transfusion of an additional RBC unit was begun. During the transfusion she developed chills, nausea, hypertension, and red-brown urine. The posttransfusion sample plasma was grossly hemolyzed with a strongly positive direct antiglobulin test (DAT) by gel. By comparison the pretransfusion plasma was normal appearing and the DAT was weaker. The eluate was negative on both occasions. Anti-Le(b) was detected in the posttransfusion sample by MTS gel (Ortho Diagnostics). Both RBC units she had received before the RBC unit that caused the reaction were Le(b+) as was the implicated RBC unit., Conclusion: This case illustrates that anti-Le(b) which is usually clinically insignificant can occasionally cause severe hemolytic transfusion reactions. Only three other reported cases of anti-Le(b) causing hemolytic transfusion reactions could be found in the literature, two of which were in abstract form only., (© 2015 AABB.)

The aim of the research is to reveal the cases of Lewis System Antigens Phenotype in West Georgia and setting the connection between antigens expressivness and IHD. Therefore, we have phenotypically tested 393 people (236 healthy donors; average age 42±7,5 and 157 patients ill with ischemic heart diseases; average age 62,5±7,5). In accordance with the findings, the number of Lewis -antigens among healthy population is 46,6% (110 ±4,8; p<0.05) with Lea-b+ phenotype; 30,9% - with Lea-b- phenotype(73±2,9; p<0.03); 19% - with Lea+b- phenotype-(47±1,7; p<0.03) Only 2,6% cases of phenotype Lea+b+ (6±0,2; p<0.02),were revealed among healthy population. As for the patients with ischemic heart diseases we got the following results: 41% cases of Lea-b- phenotype (65±3,9; p<0.05); 32,8% - Lea-b+ (51±3,2; p<0.03); 21,1% - Lea+b- - phenotype 33±2,9; p<0.03) and 5,6% - Lea+b+ phenotype (8±1,2; p<0.02). On the whole, in the West Georgia the most frequent phenotype is Lea-b+ among healthy population and Lea-b- phenotype among people with ischemic heart diseases. Research was carried out in a control group according to Lewis antigen phenotype. People were separated in two groups; I group -healthy people with Lea-b- phenotype and II group - healthy people with Lea-b+ and Lea+b- phenotypes. On the basis of the research we concluded that people in the first group (with Lea-b- phenotype) had a high BMI, arterial hypertension and lower indexes of high density lipoprotein and triglyceride than the people in the second group(with Lea-b+ and Lea+b- phenotypes. These kinds of changes (characterised to the people with Lea-b- phenotype) are associated with a high risk of ischemic diseases and atherosclerosis. To sum up, people with Lea-b- phenotype have a high risk of ischemic heart disease. In accordance with the findings, Lewis phenotype research can be carried out to detect HID and other diseases as well (hypertension, ischemic insult and insulin-dependent diabetes mellitus).

Background: Cancer patients with a Lewis (a-b-) phenotype have no carbohydrate antigen 19-9 (CA19-9) in their serum. However, we found a small but distinct elevation in the serum CA19-9 level in three cancer patients with the Lewis-negative phenotype. Here, we investigated the reason of such phenomena., Methods: Six cancer patients with a Lewis-negative phenotype were selected by very low CA19-9 concentrations: three showed a small elevation (Group A) and the other three showed no elevation (Group B) in the serum CA19-9. We investigated the difference by analyzing the Lewis/Secretor genotypes., Results: All of the six patients with a Le (a-b-) phenotype were genuine Le-negative genotypes: four individuals were homozygous for le1 (le(59,508)), one patient was compound heterozygous for le1 (le(59,508)) and le2 (le(59,1067)) and one patient was compound heterozygous for le1 and le(202,314). As for the Secretor gene, the three patients in Group B were homozygous for Se2 (one patient) or compound heterozygous for Se2 and sej (two patients), while the patients in Group A were all homozygous for sej genotypes., Conclusions: Even genuinely Le-negative patients, who genetically lack the Le enzyme and theoretically never produce CA19-9, occasionally show a slight increase in serum CA19-9 level when they are homozygous for Se-negative genotypes and suffer from advanced cancer with overproduction of glycans as precursors of CA19-9. Although such cases are not frequent, we should be acquainted with the correlation between serum CA19-9 values and genotypes of Lewis and Secretor genes.

Background: In cancer patients, MUC1 glycoprotein may carry Lewis y which could be involved in immune response., Purposes: 1- to evaluate the presence of Lewis y and MUC1 in circulating immune complexes (Lewis y/CIC and MUC1/CIC, respectively) and their correlation; 2- to analyze the possible presence of Lewis y in carbohydrate chains of tumoral MUC1 glycoprotein and 3- to correlate serum and tissue parameters considered., Methods: Pretreatment serum and tissue breast samples from 76 adenocarcinoma, 34 benign and 36 normal specimens were analyzed. Anti-MUC1 and anti-Lewis y MAbs were employed. To detect Lewis y/CIC and MUC1/CIC, ELISA tests were developed; serum samples containing MUC1 were previously selected by Cancer Associated Serum Antigen (CASA). Immunoprecipitation (IP) was performed in 9 malignant, benign and normal samples and analyzed by SDS-PAGE and Western blot. Lewis y and MUC1 expression was studied by immunohistochemistry (IHC). Statistical analysis was performed employing principal component analysis (PCA), ANOVA, Tukey HSD, Chi square test and classical correlation (p < 0.05)., Results: By ELISA, Lewis y/IgM/CIC levels showed statistically significant differences between breast cancer versus benign and normal samples; mean +/- SD values expressed in OD units were: 0.525 +/- 0.304; 0.968 +/- 0.482 and 0.928 +/- 0.447, for breast cancer, benign disease and normal samples, respectively, p < 0.05. Lewis y/IgG/CIC did not show any statistically significant difference. MUC1/IgM/CIC correlated with Lewis y/IgM/CIC. By CASA, 9 samples with MUC1 values above the cut off were selected and IP was performed, followed by SDS-PAGE and Western blot; bands at 200 kDa were obtained with each MAb in all the samples. By IHC, with C14 MAb, 47.5%, 31% and 35% of malignant, benign and normal samples, respectively, showed positive reaction while all the samples were positive with anti-MUC1 MAb; in both cases, with a different pattern of expression between malignant and non malignant samples., Conclusion: Our findings support that in breast cancer there was a limited humoral immune response through Lewis y/IgM/CIC levels detection which correlated with MUC1/IgM/CIC. We also found that Lewis y might be part of circulating MUC1 glycoform structure and also that Lewis y/CIC did not correlate with Lewis y expression.

In this study we aimed to determine the suitability of the Lewis-Y carbohydrate antigen as a target for immunotherapy using genetically redirected T cells. Using the 3S193 monoclonal antibody and immunohistochemistry, Lewis-Y was found to be expressed on a range of tumors including 42% squamous cell lung carcinoma, 80% lung adenocarcinoma, 25% ovarian carcinoma, and 25% colorectal adenocarcinoma. Expression levels varied from low to intense on between 1% and 90% of tumor cells. Lewis- was also found in soluble form in sera from both normal donors and cancer patients using a newly developed enzyme-linked immunosorbent assay. Serum levels in patients was often less than 1 ng/mL, similar to normal donors, but approximately 30% of patients had soluble Lewis-Y levels exceeding 1 ng/mL and up to 9 ng/mL. Lewis-Y-specific human T cells were generated by genetic modification with a chimeric receptor encoding a single-chain humanized antibody linked to the T-cell signaling molecules, T-cell receptor-zeta, and CD28. T cells responded against the Lewis-Y antigen by cytokine secretion and cytolysis in response to tumor cells. Importantly, the T-cell response was not inhibited by patient serum containing soluble Lewis-Y. This study demonstrates that Lewis-Y is expressed on a large number of tumors and Lewis-Y-specific T cells can retain antitumor function in the presence of patient serum, indicating that this antigen is a suitable target for this form of therapy.

Purpose: CA 19-9 is an important tumor marker in patients with pancreatic adenocarcinoma. A secondary end point of Radiation Therapy Oncology Group trial 9704 was prospective evaluation of the ability of postresectional CA 19-9 to predict survival., Methods: CA 19-9 expression was analyzed as a dichotomized variable (< 180 v > or = 180) or (< or = 90 v > 90). Cox proportional hazards models were utilized to identify the impact of CA 19-9 expression on overall survival (OS). Actuarial estimates for OS were calculated using Kaplan-Meier methods., Results: Three hundred eighty-five patients patients had assessable CA 19-9 levels. The majority had a CA 19-9 level lower than 180 or < or = 90 (n = 220 and 200, respectively), while 34% were Lewis Antigen negative and 33 (9%) and 53 (14%) patients had levels higher than 180 and higher than 90. When CA 19-9 was analyzed as a dichotomized variable, there was a significant survival difference favoring patients with CA 19-9 lower than 180 (hazard ratio [HR], 3.53; P < .0001). This corresponds to a 72% reduction in the risk of death for patients with a CA 19-9 lower than 180. This was also true for patients with CA 19-9 < or = 90 (HR, 3.4; P < .0001). Multivariate analyses confirmed that CA 19-9, when analyzed as both a continuous and a dichotomized variable, is a highly significant predictor of OS in patients with resected pancreatic cancer., Conclusion: To our knowledge, this is the first phase III trial to perform prospective analysis of CA 19-9 levels in patients treated with adjuvant chemoradiotherapy. It definitively confirms the prognostic importance of postresectional CA 19-9 levels after surgery with curative intent in patients with pancreatic cancer.

Aims: To examine a disputed association between the Lewis(a(-)b(-)) phenotype and Type 1 diabetes (T1D)., Methods: Lewis red blood cell phenotyping was performed for 97 T1D White patients and 100 control subjects using monoclonal antibodies. Two historical cohorts were also included as a control population., Results: T1D patients had a lower frequency (4.1%) of Lewis(a(-)b(-)) blood group compared with simultaneously tested healthy control subjects (10.0%) and the historical control group (11.1%, P = 0.02). Male T1D patients showed a Lewis(a(-)b(-)) frequency of 8.0%, which was similar to both matched healthy male donors (9.8%) and historical (9.5%) male control subjects. Unexpectedly, none of the female T1D patients displayed Lewis(a(-)b(-)) phenotype, vs. 10.3% and 10.8% of female control subjects (P = 0.039 and 0.017)., Conclusions: The Lewis(a(-)b(-)) phenotype occurs less frequently in T1D compared with healthy control subjects with a strong female gender bias.

Serum levels of intestinal alkaline phosphatase (IAP), a protein implicated in transcellular transport of chylomicrons, vary among ABO blood groups. In rat enterocytes, IAP is associated with chylomicron secretion, but the rat expresses only blood group A. It is not known whether chylomicron secretion may be affected in humans who express multiple blood group types. Serum samples from 40 healthy subjects were obtained after overnight fast and 3h after a high-fat meal, and assayed for IAP and apolipoprotein B-48 (apoB-48), both proteins exclusive to intestine, although only apoB-48 is found in chylomicrons. The two proteins were greater in subjects without blood antigen A (B and O) than in those with this antigen (A and AB); 2.4- and 4.7-fold for IAP and 1.5- and 2.0-fold for apoB-48 before and after the meal, respectively. Moreover, IAP and apoB-48 levels were strongly correlated in the subjects with the secretor phenotype (r > 0.81). These results indicate that IAP is strongly involved in chylomicron formation and fatty acid metabolism might change among ABO blood type. In addition, ABO blood type classification in apoB-48 measurement would improve the diagnostic value in the evaluation of metabolic syndrome.

Aim: To investigate the ABH and Lewis antigen expression in erythrocytes, saliva and gastric epithelium, as well as the association between H pylori and the presence of gastric epithelial lesions., Methods: The distribution of ABH and Lewis blood group antigens in erythrocytes, saliva and gastric mucosa of H pylori-infected gastric ulcer patients was analyzed. Forty-two patients with gastric ulcer were studied, and fifty healthy individuals were used as control group. The blood group antigens were determined by direct hemagglutination, dot-ELISA and immunohistochemical methods in erythrocytes, saliva and gastric mucosa specimens, respectively. Diagnosis for H pylori infection was performed by conventional optical microscopy and ELISA., Results: A higher seroprevalence of IgG H pylori specific antibodies was observed in gastric ulcer patients (90%) compared to the control group (60%). We observed a significant increase of phenotypes O, A2 and Lewis b in H pylori-infected patients. The expression of these antigens had progressive alterations in areas of ulcerous lesions and intestinal metaplasia., Conclusion: ABH and Lewis blood group antigens are a good indicator for cellular alterations in the gastric epithelium.

Objectives: The goal of this study was to assess the prognostic role of the Lewis antigenic system, Chlamydia pneumoniae (CP) seropositivity (CP+), and C-reactive protein (CRP) levels in unstable angina (UA)., Background: The role of CP infection in acute coronary syndromes is contradictory. The Lewis antigenic system, a genetically determined blood group system associated with infections and several disorders, including ischemic heart disease, might influence the susceptibility to CP infection, inflammatory response, and risk of cardiac ischemic events., Methods: The CRP levels, Lewis antigens, and CP+ were measured in 54 patients with Braunwald's class IIIB UA. All patients were followed up for one year, and the occurrence of new coronary events (coronary death, myocardial infarction, and recurrence of instability) were recorded., Results: Twenty-five coronary events occurred during follow-up. At univariate analysis CRP >3 mg/l (CRP+) (p = 0.0056), Lewis antigen b (Leb+) (p = 0.028), and the combination of Leb+ and CP+ (p = 0.006) and of CRP+ and Leb+ (p = 0.003) were associated with new coronary events, while CP+ alone was not. At multivariate analysis, CRP+ (p = 0.008) and combined Leb+CP+ (p = 0.03) were independent predictors of worse outcome. The event rate was 64% in CRP+ patients, 67% in Leb+CP+ patients, and 86% in CRP+Leb+CP+ patients. Combined Leb+CP+, but not Leb+ and CP+ alone, was related to CRP levels (p = 0.03). Among CP+ patients, CRP levels were higher in Leb+ than Leb- (p = 0.028)., Conclusions: Our data demonstrate that in UA the Lewis antigenic system plays an important role, probably determining individual susceptibility to the detrimental effects of CP infection and by determining an enhanced inflammatory response.

The carbohydrate antigen 19-9 (CA 19-9), a determinant (sialylated lacto-N-fucopentaose 119) of a circulating oligosaccharide antigen, is a frequently used tumor marker. Echinococcus spp. infects humans throughout the world and may be able to synthesize closely related molecules which could interfere with the measurement and interpretation of CA 19-9 concentration. The main objective of the present study was to determine the range of CA 19-9 levels in the sera of patients infected by E. granulosus (cystic hydatide disease; CYSHD) or E. multilocularis (alveolar hydatide disease; ALVHD). Serum samples were collected from patients (aged 10-85 years) over a period of 5 years: from 19 patients with CYSHD and from 20 patients with ALVHD. Infection was confirmed by positive Echinococcus serology and clinical evidence provided by imaging and/or histopathological findings. CA 19-9 was detectable in 13 patients with CYSHD (13.5 +/- 8.5 kU/l) and 13 patients with ALVHD (30.0 +/- 21 kU/l; p < 0.05). Thus ALVHD patients exhibited a significantly higher plasma level of CA 19-9 than CYSHD patients. The serum level of CA 19-9 assessed with an increased cut-off value (> 22 kU/l) was elevated in nine (45%) of 20 ALVHD patients compared to two (11%) of 19 CYSHD patients (p < 0.05). Sera from patients with Echinococcus multilocularis infection contain substances which cross-react with CA 19-9. These substances originate either from the parasite or are synthesized by the host in response to the infection, and possibly bear the Lewis-a antigen or closely related structures which are recognized by anti-CA 19-9 antibodies. Our findings are relevant to the investigation of patients presenting with cystic lesions for which the differential diagnosis includes an infectious or neoplastic origin.

Four patients with mental illness were found to be deficient in plasma alpha1,3-fucosyltransferase for the first time in Japan [Exp Clin Immunogenet 1999;16:125-130]. Complete sequencing of FUT6 genes in these individuals revealed the presence of two point mutations, i.e., G739 to A (Glu-->247 to Lys) and C945 to A (Tyr-->315 to stop). In addition to two reported alleles having G739 to A (pf1) and G739 to A and C945 to A (pf3), a new mutated allele having C945 to A (pf2) was found to be present and all the individuals who lack alpha1,3-fucosyltransferase activity in plasma were found to possess pf genes homozygously (pf/pf). In order to detect such lethal mutations in FUT6 genes easily, PCR-RFLP methods have also been developed and applied for the screening of FUT6 deficiency in a large number of samples which resulted in the demonstration of three additional FUT6-deficient individuals. The absence of alpha1,3-fucosylated molecules on alpha(1)-acid glycoprotein in plasma from all the 7 individuals was confirmed to result from the plasma alpha1,3-fucosyltransferase deficiency., (Copyright 2001 S. Karger AG, Basel.)

Lewis blood group antigen levels in human sera were assayed with a highly sensitive photothermal immunoassay which is based on laser-induced photothermal detection. Comparison of 32 colon cancer patients' sera and 34 healthy persons' sera showed that cancer patients' sera contained more Lewis antigens than healthy persons' sera. Le(a) antigen level in Le(a-) type persons and Le(b) level in Le(b-) type persons differentiated healthy persons and colon cancer patients. Furthermore, it was found that in Lewis blood phenotype (a-) several cancer patients' sera specimens changed to (a+). Many reports demonstrated that Lewis phenotype of erythrocytes changed with various conditions, including carcinomas, but they dealt mostly with erythrocytes and salivas or showed immunohistochemical evidence, and there are no reports on the quantitative analysis of ordinary (noncancerated) Lewis antigen levels in human sera. This is because Lewis antigens in sera, unlike those found in saliva, are too small to quantify with conventional immunoassay and there has been no highly selective method to measure Lewis antigens in sera. The increase of Lewis antigen in cancer patients' sera is presumed to antecede the blood type change. Our assay presented here, a highly sensitive assay of Lewis antigens, will greatly contribute to an early detection or diagnosis of cancers., (Copyright 1999 Academic Press.)

Background: Lewis phenotyping by hemagglutination is an unreliable routine method for Lewis antigen designation. Now genomic typing of the Lewis gene is available. Additionally, flow cytometry has been used for typing. We wanted to compare the results of Lewis typing in healthy individuals using the three methods., Materials and Methods: Ninety-three randomly selected plasma donors were genotyped for inactivating Secretor (FUT2) G428A and Lewis (FUT3) T59G, T202C, C314T, G508A and T1067A point mutations. All Le(a+b-) individuals (nonsecretors) were homozygous for the FUT2 G428A mutation and all Le(a-b-) individuals had inactivating mutations on both FUT3 alleles. Fixed erythrocytes were analyzed by fluorescence-activated flow cytometry and the results were compared with hem- agglutination and genotypic data. Antigen availability was expressed as median fluorescence intensity and as percentage positive cells with fluorescence intensities > or =10(2)., Results: Using an anti-Le(a) reagent a mean of 99% of erythrocytes from Le(a+b-) individuals and 1% of erythrocytes from Le(a-b-) or Le(a-b+) individuals were stained positive. Using an anti-Le(b) reagent, a mean of 71% of erythrocytes from A(1), 95% from B and 99% from O and A(2) Le(a-b+) individuals and less than 10% of erythrocytes from Le(a-b-) or Le(a+b-) individuals were stained positive. After papain treatment 100% of the erythrocytes from A(1) and A(1)B Le(a-b+) individuals stained positive without increase in background staining. The flow cytometric technique revealed large differences in staining intensities, within each ABO Le(a-b+) subgroup which was not directly correlated to plasma donation frequencies nor to Secretor or Lewis genotypes., Conclusion: Flow cytometry may prove valuable as a Lewis blood group typing technique but also as a research tool when investigating Lewis phenotypes of human erythrocytes.

Background and Study Objective: Serum sialyl Lewis X-i antigen has been shown to be one of the most specific markers for monitoring non-small cell lung cancer(NSCLC). We evaluated the correlation between serum levels of sialyl Lewis X-i antigen and mediastinal lymph node involvement in NSCLC patients., Methods: One hundred patients with untreated NSCLC were included in this study. All the patients received surgical treatment and the lymph nodes were evaluated pathologically. Pretreatment sera from these patients examined for the levels of sialyl Lewis X-i antigen, using a radioimmunoassay., Results: Serum levels of sialyl Lewis X-i antigen levels in patients with N2 were higher than those of N0-1(p = 0.0049). According to the receiver characteristic curve analysis, the recommended cut-off level of the antigen between N0-1 patients and N2 patients was 38.0 U/ml., Conclusion: Measurement of serum levels of sialyl Lewis X-i antigen might provide preoperative information in patients with NSCLC.

To evaluate the correlation between serum levels of sialyl Lewis X-i antigen and distant metastasis and survival in patients with non-small cell lung cancer (NSCLC), we measured the serum levels of the tumor marker in 371 patients with untreated NSCLC. The sialyl Lewis X-i antigen level was measured using a RIA kit. In patients with adenocarcinoma or other NSCLC subtypes, there was a correlation between serum sialyl Lewis X-i antigen and stage of the disease (P = 0.0001 and P = 0.0015, respectively). Levels of the marker varied significantly depending on the number of metastatic organs in adenocarcinoma (P = 0.0089) and in other NSCLC subtypes (P = 0.002). Univariate analysis showed that survival of NSCLC patients with high (more than 100 units/ml) sialyl Lewis X-i antigen levels was significantly poorer than that of patients with low antigen levels (P = 0.0001). Multivariate analysis using Cox's proportional hazard model showed that high sialyl Lewis X-i antigen levels correlated significantly with poor survival (P = 0.004). Our data suggest that a high serum level of sialyl Lewis X-i antigen seems to be an indicator of the presence of metastasis and might indicate the need for a careful investigation of all putative metastatic sites. The serum levels of sialyl Lewis X-i antigen may reflect the extension of metastasis and would be helpful in considering treatment options.

Prevalence of Lewis antigens and phenotypes has been investigated in 60 healthy donors and 74 patients with ischemic heart disease. It was found that phenotype Le(a-b-) marks high risk and phenotype Le(a-b+) is a resistance marker for development of ischemic heart disease. It would be valid to elucidate relationships between Lewis system and pathogenesis of internal diseases.

The major alpha3-fucosyltransferase activity in human plasma is encoded by the gene for fucosyltransferase VI (FUT6). A missense mutation (Gly-739 --> Ala) in this gene is responsible for deficiency of enzyme activity in plasma. To examine whether this fucosyltransferase is the sole enzyme responsible for the alpha3-fucosylation of serum glycoproteins in the liver, we studied the fucosylation of three glycoproteins in sera of individuals with or without inactivated FUT3 and/or FUT6 gene(s) but with a functional FUT5 gene. alpha1-Acid glycoprotein was used as the principal reporter protein for liver alpha3-fucosyltransferase activity, because of its high fucose content. In all individuals with the FUT6 missense mutation Gly-739 --> Ala in double dose, no fucosylation of alpha1-acid glycoprotein was found. This alpha1-acid glycoprotein was not intrinsically resistant to fucosylation, since it was susceptible to in vitro fucosylation using an alpha3/4-fucosyltransferase isolated from human milk. The same result was found for alpha1-antichymotrypsin and alpha1-protease inhibitor. On the other hand in all individuals with alpha3-fucosyltransferase activity in plasma, alpha3-fucosylated glycoforms of the glycoproteins studied were found. The degree of fucosylation of alpha1-acid glycoprotein was correlated with alpha3-fucosyltransferase activity (Rs = 0.82). These data indicate that the product of FUT6, but not of FUT3 or of FUT5, is responsible for the alpha3-fucosylation of glycoproteins produced in liver and suggest that this organ is a major source of alpha3-fucosyltransferase activity in plasma.

The clinicopathologic relevance of the hepatic expression of Lewis Y (Le(y)), a carbohydrate antigen, and its plasma levels was studied in benign and malignant liver diseases. Tissue and plasma antigens, respectively, were determined with an avidin-biotin-peroxidase complex method and a radioimmunoassay using monoclonal antibody AH6. Normal liver cells and bile ductules did not express Le(y). In the inflammatory tissues, the liver cells and proliferated bile ductules expressed Le(y). The strongest expression by the liver cells was observed in chronic active hepatitis with severe activity and that by the ductules in liver cirrhosis. Only 1 of 16 hepatocellular carcinomas expressed Le(y). The plasma levels of Le(y) increased significantly but nonspecifically in chronic persistent hepatitis, chronic active hepatitis, liver cirrhosis, and hepatocellular carcinomas. It was concluded that (1) Le(y) is an inflammation-associated but not a cancer-associated antigen; (2) the more the tissue damage advances, the more the antigen is expressed; and (3) hepatic and plasma Le(y) are, however, nonspecific markers of necroinflammatory liver diseases.

Survivors from meningococcal disease (serogroups B and C) and a control series (blood donors) were examined for their ability to secrete ABH blood group substance. The examination was done indirectly by determining their Lewis phenotypes. There was no significant difference in the secretor status between the two groups.

Serum levels of the tumour antigens CA 19-9 and CA-50 and their relation to the extent of the disease were studied in 97 patients with carcinoma of the pancreas. Of 13 patients with normal serum concentrations of CA 19-9, 11 (84.6%) had irresectable disease, whereas 87.5% of the patients with resectable disease expressed antigen levels above cut-off. Following attempted radical surgery, preoperatively elevated serum levels decreased in eight patients (50%). Unchanged and high levels were associated with residual disease and early death. Clinical signs of recurrence were preceded by elevated serum levels of both tumour antigens.