Receptor Antibodies In Patients Research Articles

Development of angiotensin II type 1 receptor antibodies in patients with temporary mechanical circulatory support

Development of angiotensin II type 1 receptor antibodies in patients with temporary mechanical circulatory support

Treatment with interleukin (IL)-5/IL-5 receptor antibodies in patients with severe eosinophilic asthma and COPD.

BackgroundAnti-eosinophilic therapy with interleukin-5/interleukin-5-receptor antibodies represents an established treatment for patients with severe eosinophilic asthma (SEA) but did not show clinical efficacy in patients with COPD. The objective of the present study was to evaluate treatment response to anti-eosinophilic antibody therapy in patients with asthma and COPD.MethodsA retrospective comparison of pulmonary function testing, oral corticosteroid intake, quality of life and pulmonary symptom control in patients with SEA and COPD and 1:1 propensity score matched patients suffering from SEA alone was performed. All patients received treatment with either mepolizumab or benralizumab. Data were assessed prior to antibody treatment start and after 6 months of therapy.ResultsData from 84 patients (42 patients with SEA and COPD and 42 patients with SEA) were analysed. After 6 months of treatment, patients in both groups showed improved forced expiratory volume in 1 s (improvement by 11% (IQR 5–18) in the SEA and COPD group versus 15% (IQR −3–23); p=0.637) and decreased oral corticosteroid dosages (median reduction by 3 mg in the SEA and COPD group versus 5 mg; p=0.070), without significant differences between groups. Pulmonary symptom control and quality of life improved in both groups. A significant decrease in eosinophils could be measured in both groups with similar cell numbers prior to treatment initiation (600 cells·µL−1 in the SEA and COPD group versus 500 cells·µL−1).ConclusionAnti-eosinophilic therapy with interleukin-5/interleukin-5-receptor antibodies shows clinical efficacy in patients with SEA and COPD comparable to treatment response in patients with SEA alone.

Effect of Primary Tumor Location on Second- or Later-Line Treatment With Anti-Epidermal Growth Factor Receptor Antibodies in Patients With Metastatic Colorectal Cancer: A Retrospective Multi-Center Study.

BackgroundCurrent guidelines recommend anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR Ab) as first-line treatment only in patients with left-sided RAS wild type (RASwt) metastatic colorectal cancer (mCRC). However, there are no guideline recommendations specific to tumor sidedness in subsequent-line treatment. This study aimed to investigate the effect of primary tumor location on second- or later-line treatment outcomes in patients with KRASwt mCRC.MethodsMedical records of patients diagnosed with mCRC at 3 academic centers in Thailand (Siriraj, Chulalongkorn, and Ramathibodi hospital) between 2008 and 2019 were retrospectively reviewed. Patients with KRASwt mCRC who received anti-EGFR Ab in second- or later-line treatment were included. The impact of tumor sidedness on progression-free survival (PFS) was determined using Kaplan-Meier method, and those results were compared using log-rank test.ResultsAmong the 2,102 patients who had KRAS analysis data, 1,130 (54%) patients had KRASwt. Of those, 413 patients received anti-EGFR Ab in second- or later-line treatment. One hundred and sixty-two of 413 (39%) patients had extended RAS analysis. Seventy (17%) patients had right-sided tumors. Two hundred and thirty-eight (58%) patients received anti-EGFR Ab in the third line, and 132 (32%) patients and 43 (10%) patients were treated in the second and more than third line, respectively. Single-agent irinotecan was the most commonly used backbone chemotherapy (303/413, 73%). Patients with right-sided tumors had non-significantly inferior PFS compared to patients with left-sided tumors (median PFS: 5.7 months (mo), 95% confidence interval [CI]: 3.9-7.5 vs. 7.5 mo, 95% CI 6.5-8.5; p=0.17). Subgroup analysis showed no difference in PFS when stratified by treatment lines. Patient with right-sided tumors had significantly inferior OS compared to patients with left-sided tumors (median OS: 23.3 mo vs. 29.9 mo; p=0.005).ConclusionsTo date, this is the largest real world data of the effect of primary tumor location on anti-EGFR Ab which demonstrated that tumor sidedness has no significant impact on treatment outcomes in KRASwt mCRC patients receiving second- or later-line therapy. Our findings do not support the utility of tumor sidedness for treatment selection in these settings. We confirmed that patients with right-sided tumors had significantly worse survival.

Effect of primary tumor location on second- or later-line treatment with anti-epidermal growth factor receptor antibodies in patients with metastatic colorectal cancer: A retrospective multicenter study.

195 Background: Currently, there are no guideline recommendations of anti-EGFR Ab specific to tumor sidedness in subsequent-line treatment in patients with metastatic colorectal cancer (mCRC). We previously reported the effect of primary tumor location on subsequent-line treatment with anti-EGFR Ab from a single center. Here we presented the outcome from a multi-center study. Methods: Medical records of patients diagnosed with mCRC at 3 academic centers in Thailand (Siriraj, Chulalongkorn, and Ramathibodi hospital) between 2008 and 2019 were retrospectively reviewed. Patients with KRASwt mCRC who received anti-EGFR Ab in second- or later-line treatment were included. The impact of tumor sidedness on progression-free survival (PFS) was determined using Kaplan-Meier method, and those results were compared using log-rank test. Results: Among the 2,102 patients who had KRAS analysis data, 1,130 (54%) patients had KRASwt. Of those, 413 patients received anti-EGFR Ab in second- or later-line treatment. One hundred and sixty-two of 413 (39%) patients had extended RAS analysis. Seventy (17%) patients had right-sided tumors. Two hundred and thirty-eight (58%) patients received anti-EGFR Ab in the third line, and 132 (32%) patients and 43 (10%) patients were treated in the second and more than third line, respectively. Single-agent irinotecan was the most commonly used backbone chemotherapy (303/413, 73%). Patients with right-sided tumors had non-significantly inferior PFS compared to patients with left-sided tumors (median PFS: 5.7 months (mo), 95% confidence interval [CI]: 3.9-7.5 vs. 7.5 mo, 95% CI 6.5-8.5; p =0.17). Subgroup analysis showed no difference in PFS when stratified by treatment lines. Patient with right-sided tumors had significantly inferior OS compared to patients with left-sided tumors (median OS: 23.3 mo vs. 29.9 mo; p =0.005). Conclusions: To date, this is the largest real world data of the effect of primary tumor location on anti-EGFR Ab which demonstrated that tumor sidedness has no significant impact on treatment outcomes in KRASwt mCRC patients receiving second- or later-line therapy. Our findings do not support the utility of tumor sidedness for treatment selection in these settings. We confirmed that patients with right-sided tumors had significantly worse survival.

Role of anti-phospholipase A2 Receptor antibodies in patients with membranous nephropathy: A prospective study on Indian cohort

Context: A search for a cause for membranous nephropathy (MN) is crucial to determine its treatment and management. Primary MN was a diagnosis of exclusion until the discovery of the target antigen, phospholipase A2 receptor (PLA2R). Lack of published data from the Indian population prompted this prospective study to determine the sensitivity and specificity of circulating anti-PLA2R antibodies in MN patients by using cell-based indirect immunofluorescence test (IIFT) and correlating with clinical–histopathology features and response to treatment. Settings and Design: This was a cross-sectional prospective study. Materials and Methods: MN cases (n = 34) diagnosed by renal biopsy and IIFT were evaluated along with 10 controls for serum anti-PLA2R antibodies using IIFT on biochip containing HEK 293 cell lines transfected with cDNA coded for PLA2R in this cross-sectional prospective study and simultaneously investigated to find the cause for MN. Positive cases treated with the Ponticelli regimen were followed up for 6 months with repeat testing for PLA2R. Statistics were performed using Statistical Package for Social Sciences version 18 (IBM). P < 0.05 considered significant. Statistical parameters were analyzed using the Chi-square test. Results: Anti-PLA2R antibodies-positive MN (primary MN) cases (n = 20) had higher 24-h proteinuria (10.09 ± 2.46 g) with 25% cases showing mesangial hypercellularity and basement membrane thickening in all (100%), while 50% of secondary MN cases showed mesangial hypercellularity with 7.17 ± 3.8 g of proteinuria. The sensitivity, specificity, and accuracy rate of anti-PLA2R antibodies for a diagnosis of primary MN were 70%, 100%, and 82%, respectively. Conclusion: Anti-PLA2R antibody in serum is a good reliable noninvasive diagnostic biomarker for primary MN and for monitoring its disease activity.

Характеристика окремих імунологічних показників у пацієнтів із післяопераційним рецидивом хвороби Грейвса

Актуальність. Головну роль у розвитку рецидиву гіпертиреозу відіграє активність автоімунних процесів. Багато досліджень вказують на те, що рівень антитіл до рецептора тиреотропного гормона (ТТГ) є основним чинником, який зумовлює виникнення рецидиву і може використовуватись як критерій оцінки його розвитку. Метою дослідження було вивчення клінічного перебігу, гормональних та імунологічних показників у пацієнтів із післяопераційним рецидивом хвороби Грейвса (ХГ) під час виникнення рецидиву та під час його терапії антитиреоїдними препаратами. Матеріали та методи. Групу пацієнтів становили 25 жінок віком від 23 до 73 років (у середньому 53,56 ± 2,31 року). Період часу від першого оперативного лікування до розвитку рецидиву тиреотоксикозу перебував у межах від 1 до 29 років і в середньому становив 13,33 ± 1,66 року. Результати. Рівні антитіл до рецептора ТТГ, що є основними чинниками в патогенезі ХГ, не зменшуються під час медикаментозного лікування, що вказує на безперспективність консервативної терапії післяопераційного рецидиву цього захворювання. Висновки. Після досягнення стану медикаментозної компенсації тиреотоксикозу рекомендується проведення терапії131 I чи хірургічне лікування рецидиву ХГ.

Serum levels of anti-phospholipase A2 receptor antibodies in patients with some nephrological diseases

Serum levels of anti-phospholipase A2 receptor antibodies in patients with some nephrological diseases

Positive Thyrotropin Receptor Antibodies in Patients with Transient Thyrotoxicosis

Thyrotropin (TSH) receptor antibody (TRAb) testing is considered accurate for the diagnosis of Graves disease (GD) and has been identified rarely in thyrotoxic patients without GD. We describe 4 patients with transient thyrotoxicosis and positive TRAb to highlight this clinical possibility. Patient demographics, symptoms, laboratory findings, and time to resolution of thyrotoxicosis are summarized. TRAb testing was performed by either a third-generation thyrotropin-binding inhibitory immunoglobulin (TBII) competitive-binding assay or a thyroid-stimulating immunoglobulin (TSI) bioassay from either Mayo Clinic Laboratory or Quest Diagnostics. Four patients with transient thyrotoxicosis and positive TRAb testing were identified. Of these, three were female, and the median age was 44 years (range, 25 to 49 years). Median symptom duration at evaluation was 6.5 weeks (range, 3 to 12 weeks). No patient had any clinical manifestations unique to GD or exposure to biotin, thyroid hormone, supplements, iodine, or relevant medications. The TSH was <0.1 mIU/L in all patients. Three patients had a positive TSI, which was elevated less than twice the upper limit of the reference range in all cases, and 1 patient had a strongly positive TBII. None of the patients were treated with thionamides or radioactive iodine. Spontaneous resolution occurred in all patients at a median of 5.5 weeks (range, 2 to 14.4 weeks). These cases demonstrate that TSI or TBII may be present in thyrotoxic patients with transient thyrotoxicosis. For clinically stable patients presenting without pathognomonic evidence of GD, mildly elevated TRAb results may require cautious interpretation, and alterative diagnostic testing or close monitoring should be considered. cAMP = cyclic adenosine monophosphate; FT4 = free thyroxine; GD = Graves disease; TBII = thyrotropin-binding inhibitory immunoglobulin (also known as TBI); TRAb = thyrotropin receptor antibody; TSH = thyrotropin; TSHR = thyrotropin receptor; TSI = thyroid-stimulating immunoglobulin; TT3 = total triiodothyronine; TT4 = total thyroxine.

Comparison of three competitive immunoassays for measurement of TSH receptor antibodies in patients with Graves’ disease

Thyrotropin (TSH) receptor antibodies (TRAb) mediate the hyperthyroidism of Graves’ disease (GD). The aim of the study was to compare the diagnostic performance and assay agreement between three immunoassays for the measurement of TRAb in patients with newly diagnosed GD. TRAb was measured with three different assays [H-TRAb (BRAHMS Diagnostica), M22-Man (RSR Limited) and M22-Aut (Roche Diagnostics)] in 387 participants who were recruited from two Danish population-based studies and diagnosed with GD (n = 101), multinodular toxic goitre (n = 88), primary autoimmune hypothyroidism (n = 100) or included as controls (n = 98). Coefficient of variation for duplicate measurements with each of the three assays were H-TRAb: 3.6%, M22-Man: 9.4%, M22-Aut: 7.7%. Frequency of TRAb positivity in patients with GD were H-TRAb: 95%, M22-Man: 94%, M22-Aut: 96%. Receiver operating characteristic analysis revealed a high sensitivity (H-TRAb: 95%, M22-Man: 93%, M22-Aut: 95%) and specificity (H-TRAb: 99%, M22-Man: 99%, M22-Aut: 97%) for the diagnosis of GD with all assays. Comparison of TRAb levels showed inter-assay variability and values were considerably lower with the M22-Man assay. All TRAb assays showed a high diagnostic performance for GD, but a high inter-assay variability was observed limiting the use of different assays in clinical monitoring of patients with GD.

Absence of NMDA receptor antibodies in patients with ovarian teratoma without encephalitis.

Absence of NMDA receptor antibodies in patients with ovarian teratoma without encephalitis.

A case of GABAR antibodies in schizophrenia

BackgroundIn the last couple of years, schizophrenia was often discussed as autoimmune disease. Several antibodies were suspected, but so far there has been no proof of Gamma-aminobutyric acid (GABA) receptor antibodies in patients with schizophrenia.Case presentationIn this case report we present a 21-year old woman with schizophrenic symptoms, who showed anti-GABAB1 antibodies when screened by a vast recombinant neurology mosaic on Human Embryonic Kidney Cells 293 (HEK293) cells. The young woman presented with various psychotic symptoms as well as speech and motor ataxia, with the neurological signs starting in childhood.ConclusionA hypofunction of the GABAergic system is a possible cause of severe schizophrenic symptoms. Postmortem studies proved this hypothesis by showing dysfunctional GABAergic interneurons in various brain areas. Therefore one should always think of an immune-mediated pathogenesis as well memory impairment and behavioral changes co-occur with frequent seizures.

Limbic encephalitis with phenotypic NMDA receptor antibodies in patients with de novo diagnosis of Systemic Lupus Erythematosus. Case report

Malignancy-associated limbic encephalitis was first described in 1968. Since then, cases have been reported in association with the Herpes Simplex virus, Hashimoto's encephalopathy, lupus, Sjögren's syndrome and paraneoplasias. A syndrome with prominent psychiatric symptoms was described in 2005: consisting of memory loss, reduced level of consciousness and central hypoventilation in four young women with ovarian teratoma and antibodies against an antigen highly expressed in the hippocampus.Shortly afterwards, these patients were found to have autoantibodies against NMDA receptor NR1 (GluN1) subunit. This discovery has been of the greatest importance in clinical practice since it identifies a devastating, life-threatening neurological disorder that is treatable. In 2007, it was recognised as a nosologic entity and today it is the most common cause of autoimmune encephalitis after disseminated subacute encephalomyelitis.Case report presentation of a patient exhibiting almost all the clinical symptoms described in the syndrome characterised by NMDA receptor-associated encephalitis. Moreover, a neuroradiological correlation was found, with involvement of limbic structures seen on brain magnetic resonance imaging.Reasonable exclusion was made of the presence of neoplasia and neuroinfection, and clinical and immunological criteria of systemic lupus erythemathosus were found, helping with the categorisation of lupus-associated limbic encephalitis.Mortality due to limbic encephalitis is 25%, and 75% of patients may have permanent sequelae.Given adequate response to immunosuppressive therapy, early and correct recognition are critically important.

Serum levels of various anti-Fcγ receptor antibodies in patients with systemic sclerosis

Serum levels of various anti-Fcγ receptor antibodies in patients with systemic sclerosis

Anti-NMDA receptor antibodies in patients with a first episode of schizophrenia.

BackgroundEncephalitis with antibodies against N-methyl-D-aspartate receptor (NMDA-R) is classified as an autoimmune disorder with psychotic symptoms, which are frequently dominant. However, it remains unclear how frequently NMDA-R antibodies lead to a condition that mimics psychosis and first-episode schizophrenia. In our work, we investigated the presence of antibodies against NMDA-R in patients with first-episode psychosis (FEP) in comparison with healthy volunteers.MethodsThis study included 50 antipsychotic-naïve patients with FEP (including 21 women) and 50 healthy volunteers (including 21 women). The mean age of the patients was 27.4 (±7.4) years and that of the healthy controls was 27.0 (±7.3) years. Antibodies against NMDA-R in the serum were detected by immunofluorescence.ResultsNone of the investigated patients with an FEP and none of the healthy controls showed positive antibodies against NMDA-Rs.ConclusionAccording to results of studies, a small proportion of patients with an FEP possess antibodies against NMDA-R. However, the extent to which this finding contributes to the etiopathogenesis of the response to antipsychotic medication and whether immunomodulatory therapy is indicated in these cases remains uncertain.

Anti-M3 muscarinic acetylcholine receptor antibodies in patients with primary biliary cirrhosis.

M3 muscarinic acetylcholine receptor (M3R) is expressed in biliary tracts as well as in exocrine glands. It is reported that some patients with primary biliary cirrhosis (PBC) carry autoantibodies against M3R. The aim of this study is to clarify the presence, potential use as diagnostic marker and clinical roles of anti-M3R antibodies in PBC. We synthesized peptides encoding the extracellular domains of human-M3R, including the N-terminal region, the first, second and third extracellular loops. Antibodies against these regions were examined by peptide-based enzyme-linked immunoassay in sera of 90 patients with PBC and 40 with chronic hepatitis C (CHC), 21 with non-alcoholic steatohepatitis (NASH), 10 with primary sclerosing cholangitis (PSC), 14 with obstructive jaundice, 10 with drug-induced liver injury and 42 healthy controls. Antibodies to the N-terminal, first, second and third loop were detected in 90.0% (81/90), 73.3% (66/90), 76.7% (69/90) and 66.7% (60/90) of PBC, in 67.5% (27/40), 10.0% (4/40), 67.5% (27/40) and 27.5% (11/40) of CHC, in 85.7% (18/21), 9.5% (2/21), 4.8% (1/21) and 57.1% (12/21) of NASH, in 60.0% (6/10), 20.0% (2/10), 60.0% (6/10) and 60.0% (6/10) of PSC, in 100.0% (14/14), 0% (0/14), 64.3% (9/14) and 78.6% (11/14) of obstructive jaundice, in 100.0% (10/10), 0% (0/10), 30.0% (3/10) and 10.0% (1/10) of drug-induced liver injury, and in 4.8% (2/42), 7.1% (3/42), 2.4% (1/42) and 2.4% (1/42) of the controls, respectively. A high frequency of PBC carried anti-M3R antibodies. Anti-M3R antibodies against the first loop of M3R are a potentially useful diagnostic marker for PBC.

Prevalence of anti-N-methyl-d-aspartate (NMDA) receptor antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune condition caused by immunoglobulin (Ig)G antibodies directed against the NR1 subunit of the NMDA glutamate receptor. Approximately 65% of cases present with psychiatric symptoms, particularly psychosis. It remains to be established whether anti-NMDA receptor antibodies can cause a 'purely' psychotic illness without overt neurological symptoms. We conducted a systematic literature search to establish what proportion of patients with schizophrenia and related psychoses have antibodies directed against the NMDA receptor. Studies were included if (a) subjects had a diagnosis of schizophrenia, schizophrenia spectrum disorder or first-episode psychosis (FEP) using standard criteria, (b) serum was analysed for the presence of anti-NMDA receptor antibodies; and (c) the purpose of the study was to look for the presence of anti-NMDA receptor antibodies in patients with a primary psychiatric diagnosis without clinical signs of encephalitis. Seven studies were included, comprising 1441 patients, of whom 115 [7.98%, 95% confidence interval (CI) 6.69-9.50] were anti-NMDA receptor antibody positive. Of these, 21 (1.46%, 95% CI 0.94-2.23) patients were positive for antibodies of the IgG subclass. Prevalence rates were greater in cases than controls only for IgG antibodies; other subclasses are of less certain aetiological relevance. There was significant heterogeneity in terms of patient characteristics and the antibody assay used. A minority of patients with psychosis are anti-NMDA receptor antibody positive. It remains to be established whether this subset of patients differs from antibody-negative patients in terms of underlying pathology and response to antipsychotic treatment, and whether immunomodulatory treatments are effective in alleviating psychotic symptoms in this group.

Increased Prevalence of Diverse N -Methyl-D-Aspartate Glutamate Receptor Antibodies in Patients With an Initial Diagnosis of Schizophrenia

Evidence for symptomatic convergence of schizophrenia and N-methyl-D-aspartate glutamate receptor (NMDA-R) encephalitis highlights the need for an assessment of antibody prevalence and specificity for distinct disease mechanisms in patients with a diagnosis of schizophrenia among glutamatergic pathophysiologic abnormalities in psychiatric disorders. To compare the specificity and prevalence of NMDA-R antibodies in schizophrenia (DSM-IV criteria) with those of other psychiatric diagnoses and to determine whether antibody subtypes characterize overlap with and distinction from those in NMDA-R encephalitis. Serum from 459 patients admitted with acute schizophrenia, major depression (MD), and borderline personality disorder (BLPD) or individuals serving as matched controls was obtained from our scientific blood bank. To explore epitope specificity and antibody subtype, IgA/IgG/IgM NMDA-R (NR1a or NR1a/NR2b) and α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPA-R) (GluR1/GluR2) serum antibodies were determined. Two hundred thirty matched healthy controls were compared with patients (unmedicated for at least 6 weeks) with schizophrenia (n = 121), MD (n = 70), or BLPD (n = 38). The primary outcome was the overall number of seropositive cases for NMDA-R and AMPA-R antibodies; the secondary outcome was disease specificity of IgA/IgG/IgM antibodies and epitope specificity for clinical subgroups. Diverse NMDA-R antibodies were identified in 15 subjects, primarily those with an initial schizophrenia diagnosis (9.9%), opposed to MD (2.8%), BLPD (0), and controls (0.4%). Retrospectively, 2 patients initially classified as having catatonic or disorganized schizophrenia were reclassified as having misdiagnosed NMDA-R encephalitis (presence of specific serum and cerebrospinal fluid IgG NR1a antibodies). In all other seropositive cases, the antibodies consisted of classes IgA and/or IgM or were directed against NR1a/NR2b (not against NR1a alone). None of the patients or controls had antibodies against AMPA-R. Acutely ill patients with an initial schizophrenia diagnosis show an increased prevalence of NMDA-R antibodies. The repertoire of antibody subtypes in schizophrenia and MD is different from that with NMDA-R encephalitis. The latter disorder should be considered as a differential diagnosis, particularly in young females with acute disorganized behavior or catatonia.

Anti-M3 muscarinic acetylcholine receptor antibodies in patients with Sjögren’s syndrome

Sjögren's syndrome (SS) is an autoimmune disease that affects exocrine glands including salivary and lacrimal glands. Recently, autoantibodies against muscarinic acetylcholine receptor M3 (M3R) have been detected in serum from 9 to 100% of patients with SS in addition to anti-SS-A and anti-SS-B antibodies. These observations suggest the possibility that anti-M3R antibodies could serve as a new diagnostic test in patients with SS. Some anti-M3R antibodies are directly responsible for salivary underproduction in patients with SS. Thus, strategies designed to eliminate such pathogenic antibodies could help cure SS sufferers. In this review, we summarize the current state of knowledge of anti-M3R autoantibodies in patients with SS and the correlation between B cell epitopes and the function of anti-M3R antibodies.

Acetylcholine receptor antibodies in patients with pemphigus vulgaris: Correlation with disease extent at the time of diagnosis and during follow-up

Several studies have tried to determine the relationship between autoantibodies against the acetylcholine receptor and the development of pemphigus vulgaris. In this study, we observed that antibody levels against the acetylcholine receptor are mildly elevated in pemphigus vulgaris (PV), and significantly correlate with disease severity on the initial diagnosis and during follow up. However, it is not clear if these antibodies are just an epiphenomenon or a potential trigger of the known pathogenic process in PV.

Clinical Benefit of High-Sensitivity KRAS Mutation Testing in Metastatic Colorectal Cancer Treated with Anti-EGFR Antibody Therapy

Objective: We compared high-sensitivity KRAS mutation testing with direct sequencing for predicting the efficacy of antiepidermal growth factor receptor antibodies in patients with metastatic colorectal cancer (mCRC). Methods: We analyzed the KRAS status in 61 tumors from cetuximab-treated mCRC patients by both direct sequencing and a high-sensitivity method: 2-step PCR restriction fragmentation length polymorphism (RFLP). Therapeutic effects in each mutational status were evaluated. Results: The incidences of KRAS mutations determined by direct sequencing and 2-step PCR RFLP were 34.4 and 52.5%, respectively (p = 0.02). Patients were categorized into 3 groups [W/W, wild-type by both methods (n = 29); W/M, wild-type by direct sequencing, detected mutation by 2-step PCR RFLP (n = 11); M/M, mutant-type by both methods (n = 21)]. The response rate for cetuximab in the W/M group (0%) was the same as that in the M/M group, and was significantly lower than in the W/W group (41.4%) (p < 0.001). Progression-free survival in the W/M group (11.0 weeks) was similar to that in the M/M group (8.0 weeks), and was significantly shorter than in the W/W group (18.0 weeks) (p < 0.002). Conclusion: High-sensitivity KRAS mutation testing is useful for selecting true responders to cetuximab.