scholarly journals The Lavender Way – Lavender Procedure, A Way to Defeat Breast Cancer Without Surgery: Chemotherapy or Radiation

2021 ◽  
pp. 1-12
Author(s):  
Phillip Bretz ◽  
Phillip Bretz ◽  
Richard Lynch ◽  
David Mantik
Keyword(s):  
Breast Cancer ◽  
Local Recurrence ◽  
Normal Activity ◽  
Second Primary ◽  
Breast Cancers ◽  
Psychological Burden ◽  
Group Iii ◽  
Small Breast ◽  
Group I ◽  
Group Ii

Background: Despite advances in metabolic pathways, exosomes, ct-DNA, biomarkers, and imaging technology, breast cancer is still with us. It is a global curse, with incidence set to double in the U.S. by 2030. Increasingly, researchers blame this debacle on our persistent use of unreliable preclinical testing with mouse models. Further, while basic science understanding has exploded, we know each daughter cell is genetically different, with likely increased resistance to therapy – and increased aggressiveness. Nonetheless, our current approach requires killing every one of these daughters to the last. The authors have devised a new game plan; the new goal is to kill the very first cells, not the last ones. This can be implemented globally – with dramatic cost reduction, and more lives saved while leaving the breast intact. Methods: The authors have created The Lavender Way, which employs multiple non-radiation diagnostic modalities. This allows us to predict within ten years in a person's lifetime when breast cancer will likely manifest. Then imaging is accelerated with modified military Infrared, ultrasound, and others to locate ultra-small breast cancers (5-8mm). Tumor analysis can determine each tumor’s aggressiveness. Via a 20-minute office procedure under local anaesthesia (i.e., Cryoablation, aka The Lavender Procedure), the tumor can be killed with the patients resuming normal activity immediately. It is both a dramatic change in treatment and, just as significant, a dramatic change in lifting the psychological burden of this dreaded disease. Results: Group I: Ideal Patients, Group II: Less than Ideal, Group III: Strictly Palliative. All in Group I are alive after seven years except one. That one died of a fall, cancer-free, and one is alive with a local recurrence successfully treated with repeat cryoablation. Group II had one local recurrence, and one had a second primary tumor in a different location in the breast. Group III refused any other treatment and had metastatic disease. They were treated to prevent tumors from eroding through the skin. Most have died. The Lavender Way paves the way for The Lavender Procedure. Conclusion: Ultra-small breast cancers with optimal bio-markers are ideal candidates for The Lavender Procedure (i.e., Cryoablation). All patients resumed normal activity immediately – without sutures. All patients in Group I and II patients have avoided surgery, chemotherapy, and radiation.

scholarly journals The Lavender Way – Lavender Procedure - A Way to Defeat Breast Cancer Without Surgery, Chemotherapy or Radiation A Clarion Call for Radical Change

2021 ◽  
Vol 2 (2) ◽  
Author(s):  
Phillip Bretz ◽  
BG Richard Lynch ◽  
David Mantik
Keyword(s):  
Breast Cancer ◽  
Local Recurrence ◽  
Normal Activity ◽  
Second Primary ◽  
Breast Cancers ◽  
Psychological Burden ◽  
Group Iii ◽  
Small Breast ◽  
Group I ◽  
Group Ii

Background Despite advances in metabolic pathways, exosomes, ct-DNA, biomarkers, and imaging technology, breast cancer is still with us. It is a global curse with incidence set to double in the U.S. by 2030. Increasingly, researchers blame this debacle on our persistent use of unreliable preclinical testing with mouse models. Further, while basic science understanding has exploded, we know each daughter cell is genetically different, with likely increased resistance to therapy - and increased aggressiveness. Nonetheless, our current approach requires killing every one of these daughters to the last. The authors have devised a new game plan; the new goal is to kill the very first cells, not the last ones. This can be implemented globally - with dramatic cost reduction, and more lives saved while leaving the breast intact. Methods The authors have created The Lavender Way, which employs multiple non-radiation diagnostic modalities. This allows us to predict within ten years in a person's lifetime when breast cancer will likely manifest. Then imaging is accelerated with modified military Infrared, ultrasound, and others to locate ultra-small breast cancers (5-8mm). Tumor analysis can determine each tumor’s aggressiveness. Via a 20-minute office procedure under local anesthesia (i.e., Cryoablation, aka The Lavender Procedure), the tumor can be killed with the patients resuming normal activity immediately. It is both a dramatic change in treatment and, just as significant, a dramatic change in lifting the psychological burden of this dreaded disease. Results Group I - Ideal Patients Group II – Less than Ideal Group III – Strictly Palliative All in Group I are alive after seven years except one. That one died of a fall, cancer-free, and one is alive with a local recurrence successfully treated with repeat cryoablation. Group II had one local recurrence, and one had a second primary tumor in a different location in the breast. Group III refused any other treatment and had metastatic disease. They were treated to prevent tumors from eroding through the skin. Most have died. The Lavender Way paves the way for The Lavender Procedure Conclusion Ultra-small breast cancers with optimal bio-markers are ideal candidates for The Lavender Procedure (i.e., Cryoablation). All patients resumed normal activity immediately – without sutures. All patients in Group I and II patients have avoided surgery, chemotherapy, and radiation.

scholarly journals Sonographic Study of Female Pelvic Organs in Breast Cancer Patients Taking Tamoxifen: Clinical Correlation

2020 ◽  
Vol 7 (1) ◽  
pp. 17-23
Author(s):  
Rafia Parveen ◽  
Shaikh Shofiur Rahman ◽  
Taposhi Sarker ◽  
Syed Muhammad Baqui Billah ◽  
Zakir Hossain Habib
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Endometrial Thickness ◽  
Tamoxifen Therapy ◽  
Tamoxifen Treatment ◽  
Breast Cancer Patients ◽  
Group Iii ◽  
Group I ◽  
Group Ii ◽  
Uterine Volume

Background: As most of breast cancer patients are treated with Tamoxifen, different effects of this drug in patients should be evaluated since no such study is carried out in Bangladesh till date. Objective: The purpose of the present study was to evaluate sonographic changes of female genital organs in breast cancer patients treated with Tamoxifen and to correlate these changes with duration of Tamoxifen treatment and gynecological symptoms. Methodology: This randomized double-blind clinical trial was carried out in Delta Medical College Hospital, Dhaka, Bangladesh from May 2017 to April 2018 for a period of one (1) year. The participants were breast cancer patients which were divided into three groups named as group I patients. The patients of these group were on Tamoxifen therapy. The patients of group II were without Tamoxifen therapy. The patients of group III had completed Tamoxifen therapy. All participants underwent ultrasonography. Results: Patients receiving Tamoxifen therapy had significantly more thickened endometrium compared to other groups (26.6% in group I, 5% in group II and3% in group III). Similarly, abnormal sonographic findings and mean uterine volume were higher in group I compared to other two groups. Endometrial thickness and uterine volume showed significant positive correlation with duration of Tamoxifen therapy (p <0.0001). The endometrial thickness and uterine volume greatly increased after two years of Tamoxifen therapy while it was reverse in group III. Gynecological symptoms had no significant relations with sonographic abnormalities and thickened endometrium. Conclusion: Tamoxifen therapy is associated with increased endometrial thickness, uterine volume and abnormal sonographic findings, compared to patients without Tamoxifen or completing Tamoxifen therapy. Journal of Current and Advance Medical Research 2020;7(1): 17-23

Does administration of chemotherapy before radiotherapy in breast cancer patients treated with conservative surgery negatively impact local control?

1995 ◽  
Vol 13 (12) ◽  
pp. 2906-2915 ◽  
Author(s):  
C E Leonard ◽  
M E Wood ◽  
B Zhen ◽  
J Rankin ◽  
D A Waitz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Local Recurrence ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Conservative Surgery ◽  
Breast Cancer Patients ◽  
Group I ◽  
Group Ii ◽  
Prolonged Surgery

PURPOSE To determine if a delay of irradiation to the intact breast for administration of adjuvant chemotherapy results in increased local recurrence in breast cancer. PATIENTS AND METHODS The records of 262 women with 264 cases of breast cancer were reviewed. Group I contained 105 patients treated with conservative surgery, chemotherapy, and radiotherapy. Group II contained 157 patients (used as a concurrent control) treated with conservative surgery and radiotherapy only. Eighty-nine percent of subjects in group I received all chemotherapy before radiotherapy. Fifty-eight percent of patients received hormone therapy. Seventy-one percent of patients had negative surgical margins, and 74% had negative lymph nodes. For group I, conservative surgery-radiotherapy intervals in months were less than 1 (five, 5%), > or = 1 to less than 3 (10, 9%), > or = 1 to less 6 (48, 46%), and > or = 6 (42, 40%), mean of 5. For group II, the intervals were less than 1 (20, 13%), > or = 1 to less than 3 (123, 79%), > or = 3 to less than 6 (11, 7%), and > or = 6 (two, 1%), mean of 1.5. RESULTS Thirty patients (11.5%) have disease recurrence (19 distant [6%] and 12 local [5%]). There were no significant differences in local recurrence (group I, four [4%]; group II, eight [5%]; difference not significant). There were no significant differences in local recurrence in any surgery-radiotherapy interval within each group. Although we found marginal increases in the percentage of local recurrences in group I patients (with prolonged surgery-radiotherapy intervals) who had positive margins, positive lymph nodes, and tumor size more than 2 cm versus group II (without prolonged surgery-radiotherapy intervals), these results were not significant. CONCLUSION We could not identify any surgery-radiotherapy interval that resulted in increased local recurrence if radiotherapy was delayed for administration of adjuvant chemotherapy in breast cancer patients. Because of the heterogenous population of breast cancer patients, our results also support the need for further study to determine the optimum integration of radiotherapy and chemotherapy in the management of the conservatively treated breast.

scholarly journals Eπώδυνες οστικές μεταστάσεις

2013 ◽  
Author(s):  
Παναγιώτης Σιδεράς
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Pain Relief ◽  
Karnofsky Performance Scale ◽  
Pain Palliation ◽  
Group Iii ◽  
Group I ◽  
Group Ii ◽  
Grade Iii

Aim: The consecutive administration of two different bone seeking radio-pharmaceuticals such as 186Re-HEDP and 89Sr-Cl was compared with 89Sr-Cl plus chemotherapy and 186Re-HEDP alone were investigated to determine the effectiveness and toxicity in pain palliation of bone metastases in patients with prostate, breast and lung cancer.Material and Methods: The effect of treatment with consecutive infusions with 186Re-HEDP and 89Sr-Cl was compared with 89Sr-Cl plus chemotherapy and 186Re-HEDP alone on pain symptoms, quality of life and bone marrow function. In total, we treated 32 patients of which 11 (Group I) were treated (5 men with prostate cancer and 6 women with breast cancer) with consecutive infusions with 186Re-HEDP and 89Sr-Cl, 12(Group II) were mostly men with prostate cancer that received 89Sr-Cl plus chemotherapy and 9 patients (Group III) 6 women with stage IV breast cancer, 1 man with lung cancer and 2 men with hepatocellular cancer with 186Re-HEDP alone. The follow up period was 16 weeks. In Group I the patients received an infusion of 186Re-HEDP [(dose of 1200MBq (32.4 mCi) ±96.21 MBq (2.6mCi)] followed by bi-weekly blood counts until 8 weeks to measure myelotoxicity. At the end of this period 89Sr-Cl was infused at a dose of 137 MBq (3.7mCi) ± 3.63MBq (0.098mCi) followed in the same manner with bi-weekly measurement in blood counts to estimate overall patient responsiveness to therapy, increase in performance and toxicity. In Group II all patients received a standard dose of 89Sr-Cl [148MBq(4 mCi) ± 2.2 MBq (0.06 mCi). In Group III all patients received a standard 186Re-HEDP dose of 1480 MBq (40 mCi) ± 3.7MBq (0.01 mCi) and Zolendronate. All patients were interviewed using standardized form of questions before and after therapy weekly for 16 weeks.Results: In Group I 91%(10/11) of the patients reported pain relief after the end of 16 weeks whereas 18% (2/11) reported discontinuation of their analgesics and remained pain-free. Pain showed a decrease from 7.8±1.7 to a value of 2.8±1.2 on a visual analogue scale (p<0.0001). Patients also described an improvement on Karnofsky performance scale from 68±6 to 79±4 (p<0.005), 16 after completion of therapy. Myelotoxicity was observed in 2 patients (18%) manifesting as thrombocytopenia grade III, 4(36%) stage II and 5(45%) as stage I. The maximum nadir of platelets and leukocyte counts were observed at the end of 4 weeks of each therapy and was completely reversible at the end of each therapy. In Group II which was comprised mainly from prostate cancer patients 67%(8/12) reported pain relief at the end of 16 weeks with only 1 patient (8%) discontinued all analgesics. Pain score on VAS decreased from 8.3±1.8 to 3.7±1.7 (p<0.0001), improvement on Karnofsky performance scale was from 75 to 80. Myelotoxicity was seen in 4/12 (33%) of the patients and this could be attributed likely to the combined affect of chemotherapy and radioisotope treatment manifesting as grade III thrombocytopenia, grade II in 6/12 (50%) and only in 2/12 (16%) as grade I. In group III, which appeared a slightly more heterogenous than the other two groups, 1 lung cancer patient expired within the 16 weeks of follow up likely secondary to type I respiratory failure and 1 patient with hepatocellular carcinoma was lost to follow up. All other patients mainly breast cancer showed adequate analgesia with decrease of pain on VAS from 8.2±1.3 to 4.1±1.9 (p<0.008) with none discontinuing all analgesics. Improvement on Karnofsky scale was recorded as 75-80(p>0.2). Myelotoxicity was seen in 2/9 (22%) manifesting as grade III thrombocytopenia, 4/9 (44) as grade II and 3/9 (33%) as grade I.Conclusion: All radiopharmaceuticals used either consecutively or in combination with chemotherapy or alone were effective in metastatic bone pain palliation. There was no significant induction of Myelotoxicity except with a percentage of 33% seen in 89Sr-Cl plus chemotherapy group. In this small prospective study we achieved bone pain palliation with consecutive administration of 2 different radiopharmaceuticals. We modified slightly the dose of 186Re-HEDP such as to avoid serious and potentially lethal myelotoxicity. We achieved a greater and longer analgesic response as compared to the other two groups based on the fact that faster induction of analgesia was attained with the relatively low beta emitter 186Re-HEDP and greater pain relief with a longer duration of pain control the high beta emitter 89Sr-Cl.

scholarly journals Better survival associated with successful vitamin D supplementation in non-metastatic breast cancer survivors

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Elif Isbilen ◽  
Tulay Kus ◽  
Havva Yesil Cinkir ◽  
Gokmen Aktas ◽  
Aysegul Buyukbebeci
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Disease Free Survival ◽  
Vitamin D Supplementation ◽  
Group Iv ◽  
Free Survival ◽  
Group Iii ◽  
Risk Of Death ◽  
Group I ◽  
Group Ii

Abstract Background We aimed to clarify whether successful vitamin D supplementation could predict improved survival in breast cancer (BC) survivors after completion of adjuvant treatment. Materials and Methods Patients were classified into four groups based on changes of 25(OH)D level during the treatment follow-up. Log-rank statistics were used to compare survival distributions among groups. ORs and 95% CIs were given for mortality ratios. Results The risk of death in group II with low 25(OH)D levels was 4.2 times higher than in group I with high 25(OH)D levels. (OR = 4.17 (95% CI = 1.46–11.91), P = 0.008) and the risk of death in group IV whose 25(OH)D levels never increased was 4.3 times higher (OR = 4.29 (95% CI = 1.13–16.3)). According to the log-rank test, life expectancy was significantly higher in group II compared to group I (P = 0.017) and group III (P = 0.001). Group IV had significantly lower survival times than group III (P = 0.021). Conclusions Vitamin D supplementation may play an important role in the response of the received treatments and provide a lower mortality rate and better overall -free survival (OFS) and disease-free survival (DFS) to BC patients. However, we observed a sign of poorer BC survival still after sufficient vitamin D supplementation.

Real-world clinical analysis and overall survival-related biomarker of breast cancer (BC) patients under 35 years old.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12569-e12569
Author(s):  
Jinpu Yu ◽  
Yang Li ◽  
Xuesong Li ◽  
Beibei Yang ◽  
Shuaibing Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Targeted Therapy ◽  
Deep Sequencing ◽  
Similar Proportion ◽  
Cancer Genes ◽  
Group Iii ◽  
Pathological Type ◽  
Group I ◽  
Group Ii

e12569 Background: Breast cancer (BC) is one of the most common malignant tumors among women in the world. Although under 7% of all BC cases, young BC is more difficult to diagnose and can be aggressive and less likely to respond to treatment. Exploring and identifying potential biomarkers for the diagnosis and prognosis of younger BC patients is necessary. Methods: A total of 1,202 BC patients under 35 years old (YD) were enrolled. Deep sequencing targeting 450 cancer genes was performed in a laboratory accredited by College of American Pathologists (CAP) and certified by Clinical Laboratory Improvement Amendments (CLIA) for genomic alteration identification. Statistical analysis was performed by Fisher’s exact test. Results: Of 1,202 young BC patients, 3 were under 20 YD, 85 were 20-25 YD, 371 were 26-30 YD, and 747 were 31-35 YD. Based on pathological, there were 899 infiltrative duct carcinomas, 10 infiltrative lobular carcinomas, and 292 BCs with unclear pathological type. According to molecular features, 587 HR+/HER2- (group I), 118 HR+/HER2+ (group II), 75 HR-/HER2+ (group III) and 193 HR-/HER2- (group IV) were included. Chemotherapy, radiotherapy, endocrine therapy and targeted therapy were received and 1074 patients were followed up. The median overall survival (OS) was 76 (5-156) months. There was no significant difference in OS between different treatments. The median OS was 81 (range 5-156) months, 67 (range 10-153) months, 76 (range 14-146) months, and 78 (range 13-151) months for group I, II, III, and IV, respectively. The significantly lower OS was observed in group II ( P=0.044). Although group II and group III had similar proportion of targeted treatment (43.22% vs 43.24%, respectively), the OS rate was different (67 vs 76 months, P=0.064). Samples from 46 young BC patients were performed on deep sequencing targeting 450 cancer genes. The most common mutations were TP53 (56%), GATA3 (29%), ERBB2 (27%), CDK12 (20%), and FGFR1 (20%). Different from previous studies, only 4.35% (2/46) of BRCA1/2 mutations were detected in this cohort. The mutation frequency of GATA3 in group II was significantly lower than that in group III (0% vs 71.43%, P=0.017). Conclusions: The most common pathological type of young BC was infiltrative duct carcinoma. The OS of HR+/HER2+ patients were significantly lower than that of others. Our results showed that GATA3 could be a potential biomarker for OS prediction for BC with HER2+, which help to further guide targeted therapy in young BC patients.

Effect of Delay in Initiation of Adjuvant Trastuzumab and Dose Interruptions on Overall Treatment Outcome in Breast Cancer Patients, a Retrospective Study

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Atef Youssef Riad ◽  
Azza Mohammed Adel Alkhateeb ◽  
Mohammed Reda Kelany ◽  
Mohammed Al-Saeed Sakran Ali Al-Shater
Keyword(s):  
Breast Cancer ◽  
Progression Free Survival ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
University Hospitals ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Group I ◽  
Group Ii ◽  
The Impact

Abstract Background HER2 amplification or protein over-expression is found in 20% of invasive breast cancers. It’s clearly associated with accelerated cell growth and proliferation and poor clinical outcome. The amplification of HER2 was historically an adverse prognostic factor associated with a higher risk of recurrence, lack of or lower levels of ER expression, and relative resistance to endocrine therapy and CMF based chemotherapy. Objectives We aimed in this study to assess the impact of delaying the initiation of adjuvant Trastuzumab for more than three months after the diagnosis of breast cancer and the effect of irregular and interrupted doses of adjuvant Trastuzumab, on progression free Survival, relapse, and overall survival (OS) among patients with breast cancer. Patients and Methods A Retrospective cohort study was conducted in Ain Shams University Hospitals. The study included one hundred patients with HER2 positive breast cancer. from January 2011 till December 2016 at the" Department of Clinical Oncology and Nuclear Medicine, Ain Shams University Hospitals". Results The median time to progression in group I was 19 months compared to 30 months in group II. There was statistically significant decrease median of group I compared to group II according to PFS. Conclusion We concluded that delays in the initiation of adjuvant treatment may be particularly harmful in patients with more aggressive tumor types.

The effects of royal jelly on the oxidant-antioxidant system in rats with N-methyl-N-nitrosourea-induced breast cancer

2017 ◽  
Vol 43 (2) ◽  
pp. 176-183 ◽  
Author(s):  
Meltem Malkoç ◽  
Diler Us Altay ◽  
Ahmet Alver ◽  
Şafak Ersöz ◽  
Tuğba Mazlum Şen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Royal Jelly ◽  
Protein Carbonyl ◽  
Develop Breast Cancer ◽  
Control Group ◽  
Sprague Dawley ◽  
Group V ◽  
Group Iii ◽  
Group I ◽  
Group Ii

AbstractObjectives:To determine the effect of royal jelly (RJ) on the oxidant-antioxidant balance in rats with N-methyl-N-nitrosourea (MNU) induced breast cancer and to compare this with the chemotherapeutic agent paclitaxel.Material and methods:Fifty-six female Sprague Dawley rats were divided into five groups. Except control group (n=8, Group I) others received MNU (50 mg/kg, a single dose, i.p.) to develop breast cancer: Group II (n=8) untreated, Group III (n=7) treated with paclitaxel (15 mg/kg/week, 3 times, i.p.), Group IV (n=7) with RJ (by oral gavage, 100 mg/kg/day, for 30 days), and Group V (n=7), with paclitaxel+RJ. At the end of 30 days, histopathological and biochemical parameters were evaluated in breast tissues.Results:Levels of protein carbonyl (PC) and 8-hydroxy-deoxyguanosine (8-OHdG) were higher in Group V than in Group II while malondialdehyde (MDA) levels were lower in groups IV and V compared to Group II (p<0.05). Levels of catalase (CAT) in Group V and glutathione (GSH) in Group III were higher than Group II (p<0.05). Glutathione peroxidase (GPx) and superoxide dismutase (SOD) levels did not significantly different. Decreasing effect of RJ on CA15-3 levels was relevant to histopathological results.Conclusion:Although RJ (with or without paclitaxel) had increasing effect of antioxidant status it was insufficient to reduce oxidative stress in breast cancer.

Ultrastructural Lesions Produced by Alcohol and Sucrose in the Heart and Liver of C57BL Mice

1970 ◽  
Vol 28 ◽  
pp. 208-209
Author(s):  
K.K. SEKHRI ◽  
C.S. ALEXANDER ◽  
H.T. NAGASAWA
Keyword(s):  
Osmium Tetroxide ◽  
Male Mice ◽  
Alcohol Group ◽  
Group Iii ◽  
Group I ◽  
C57bl Mice ◽  
Group Ii

C57BL male mice (Jackson Lab., Bar Harbor, Maine) weighing about 18 gms were randomly divided into three groups: group I was fed sweetened liquid alcohol diet (modified Schenkl) in which 36% of the calories were derived from alcohol; group II was maintained on a similar diet but alcohol was isocalorically substituted by sucrose; group III was fed regular mouse chow ad lib for five months. Liver and heart tissues were fixed in 2.5% cacodylate buffered glutaraldehyde, post-fixed in 2% osmium tetroxide and embedded in Epon-araldite.

Heterogeneity and Immunochemical Properties of Anti-β2-glycoprotein I Autoantibodies

1998 ◽  
Vol 80 (09) ◽  
pp. 393-398 ◽  
Author(s):  
V. Regnault ◽  
E. Hachulla ◽  
L. Darnige ◽  
B. Roussel ◽  
J. C. Bensa ◽  
...  
Keyword(s):  
Fluid Phase ◽  
Anticardiolipin Antibodies ◽  
Dual Reactivity ◽  
Group Iii ◽  
Important Group ◽  
Epitope Specificity ◽  
Glycoprotein I ◽  
Group I ◽  
Group Ii ◽  
Sufficient Concentration

SummaryMost anticardiolipin antibodies (ACA) associated with antiphospholipid syndrome (APS) are directed against epitopes expressed on β2-glycoprotein I (β2GPI). Despite a good correlation between standard ACA assays and those using purified human β2GPI as the sole antigen, some sera from APS patients only react in the latter. This is indicative of heterogeneity in anti-β2GPI antibodies. To characterize their reactivity profiles, human and bovine β2GPI were immobilized on γ-irradiated plates (β2GPI-ELISA), plain polystyrene precoated with increasing cardiolipin concentrations (CL/β2GPI-ELISA), and affinity columns. Fluid-phase inhibition experiments were also carried out with both proteins. Of 56 selected sera, restricted recognition of bovine or human β2GPI occurred respectively in 10/29 IgA-positive and 9/22 IgM-positive samples, and most of the latter (8/9) were missed by the standard ACA assay, as expected from a previous study. Based on species specificity and ACA results, IgG-positive samples (53/56) were categorized into three groups: antibodies reactive to bovine β2GPI only (group I) or to bovine and human β2GPI, group II being ACA-negative, and group III being ACA-positive. The most important group, group III (n = 33) was characterized by (i) binding when β2GPI was immobilized on γ-irradiated polystyrene or cardiolipin at sufficient concentration (regardless of β2GPI density, as assessed using 125I-β2GPI); (ii) and low avidity binding to fluid-phase β2GPI (Kd in the range 10–5 M). In contrast, all six group II samples showed (i) ability to bind human and bovine β2GPI immobilized on non-irradiated plates; (ii) concentration-dependent blockade of binding by cardiolipin, suggesting epitope location in the vicinity of the phospholipid binding site on native β2GPI; (iii) and relative avidities approximately 100-fold higher than in group III. Group I patients were heterogeneous with respect to CL/β2GPI-ELISA and ACA results (6/14 scored negative), possibly reflecting antibody differences in terms of avidity and epitope specificity. Affinity fractionation of 23 sera showed the existence, in individual patients, of various combinations of antibody subsets solely reactive to human or bovine β2GPI, together with cross-species reactive subsets present in all samples with dual reactivity namely groups III and II, although the latter antibodies were poorly purified on either column. Therefore, the mode of presentation of β2GPI greatly influences its recognition by anti-β2GPI antibodies with marked inter-individual heterogeneity, in relation to ACA quantitation and, possibly, disease presentation and pathogenesis.

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