CCP Test Research Articles

Comparison of whole slide image–based deep learning algorithms and genomic classifiers for assessing the risk of prostate cancer metastasis in surgically treated patients.

344 Background: Genomic classifiers improve post-radical prostatectomy (RP) risk stratification compared to conventional clinical-pathologic parameters, but are tissue-destructive and expensive. In contrast, artificial intelligence algorithms utilizing diagnostic hematoxylin and eosin (H&E)-stained slides for risk stratification conserve tissue and could be made widely available at point-of-care. We compared the predictive output of a deep learning-based algorithm applied to H&E-stained whole slide images (WSI) of prostate tumors to commercial genomic classifiers such as Decipher and Prolaris in three diverse RP cohorts with follow-up for metastasis. Methods: We used subsets of three previously published Johns Hopkins RP cohorts with available genomic classifier data. The Natural History Cohort (n=249, Decipher test, PMID: 26058959) and Case-Cohort (n=210, Prolaris CCP test, PMID: 36006048) both utilized a case-cohort design on the outcome of metastasis and consisted of predominantly self-identified White patients, while the Race Cohort (n=93, Decipher test, PMID: 31969336) included only self-identified Black patients with clinical follow-up. For each cohort, a single representative H&E-stained slide from the dominant tumor nodule at RP was scanned. The DL algorithm utilized tumor detection in H&E-stained WSI followed by a classification model to predict metastasis, with or without clinical parameters (age, race, pre-operative PSA, pathologic T- and N-stage, and margin status). The algorithm was trained (n=197) and validated (n=52) on patients from Natural History Cohort and tested on the Race Cohort and Case-Cohort. Harrell’s C-indices based on unadjusted Cox models for time to metastasis were evaluated. Results: The C-index for the WSI-based deep learning algorithm on the Natural History Cohort validation subset was 0.766 (95% confidence interval [CI]: 0.730-0.802) compared to 0.732 (95% CI:0.698-0.766) for the Decipher score. The C-index for WSI-based deep learning algorithm in the Race Cohort was 0.804 (95% CI: 0.790-0.818) compared to 0.724 (95% CI: 0.721-0.726) for the Decipher score. The C-index for the WSI-based deep learning algorithm in the Case-Cohort was 0.840 (95% CI: 0.829-0.851) compared to 0.801 (95% CI: 0.800-0.802) for the Prolaris CCP score. The C-index values for the deep learning algorithm utilizing WSI plus clinical-pathologic parameters were 0.836 (95% CI: 0.796-0.876), 0.882 (95% CI: 0.869-0.894), and 0.890 (95% CI: 0.878-0.901) for the Natural History Cohort, Race-Cohort, and Case-Cohort, respectively. Conclusions: DL algorithms utilizing WSI with or without clinical-pathologic parameters outperform currently employed genomic classifiers for the prediction of metastasis. Validation in additional multi-institutional and racially diverse cohorts is underway.

The Relationship Between Helicobacter pylori Infection and Development of Rheumatoid Arthritis

Background : Helicobacter pylori is a spiro-helical, gram-negative & microaerophilic bacteria that particularly lives in the stomach. It has helix form is thought to have developed to puncture the mucoid lining of the stomach and transmit infection. Almost around world about half of population infected with these bacteria, which is broadly dispersed. The interplay of genetic predisposition and environmental exposures results in autoimmune disorders. Infectious triggers have been linked and thoroughly explored among environmental exposures.
 Purpose: To identify the frequency of peoples infected with Helicobacter pylori with autoimmune disorders like rheumatoid arthritis and to determine how this infection may affect the immune system and contribute to autoimmune disease.
 Methods: 100 Stool samples were collected from patients (50) & control group (50) having mild to severe abdominal symptoms also they have pain in joints and bones in order to detect H. pylori infection by stool antigen (Ag) test also urea breath test done to confirm the diagnosis , the patients also diagnosed for rheumatoid arthritis (RA) via anti -CCP test by blood samples collection .
 Results: 50 total patients were infected by H. pylori , Females have higher rate of infection with 60% and males 40% . (40-49) years old age patients have higher rate of infection . (30%) of patients with positive H. pylori and chronic gastritis suffered from Pain in bones and joints and diagnosed with RA , while only 6 % of controls without H. pylori infection diagnosed with RA and showed less gastrointestinal symptoms and no joints inflammation.
 Conclusions: In our study we can conclude that there is a strong association between gastritis in patients caused by helicobacter pylori and development of autoimmune diseases represented by rheumatoid arthritis .

COMPARISON OF RHEUMATOID FACTOR (RF) AND ANTI CYCLIC CITRULLINATED PEPTIDE (ANTI -CCP) ANTIBODIES IN EARLY DIAGNOSIS OF RHEUMATOID ARTHRITIS.

Background: Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammation of joints causing deformities and functional impairment. Rheumatoid factor (RF) is an autoantibody specific for the Fc portion of human IgG. RF has low specificity as high false positive results are common in the general population. Anti CCP (Anti-cyclic citrullinated peptide) antibody is also a useful marker to diagnose rheumatoid arthritis and included in one of the criteria of the American College of Rheumatology (ACR) /European League against Rheumatism (EULAR) classification of RA. This study is done to compare the diagnostic utility of Anti CCP and RF test in RA patients. Aim & Objective: Comparison of rheumatoid factor (RF) and Anti cyclic citrullinated peptide (Anti -CCP) antibodies in diagnosis of rheumatoid arthritis- in a tertiary care hospital. Material &Methods: A total of 70 samples were taken from clinically suspected RA patients over a period of 6 months.RF and AntiCCP was checked in all patients Results &Discussion: Out of total 70 samples tested, 51 were seropositive with only Anti CCP positive were 37 (52%) and only RF positive were 6 (8.5%), whereas both Anti CCP and RF positive both positive were 8 (11.4%) Conclusion: Anti CCP antibody test and RF can be used mutually for early diagnose of Rheumatoid arthritis and suitable management can be initiated to decrease future morbidity.

What is The Economic Impact of CCP Test Misclassification in Rheumatoid Arthritis Diagnosis? A Benchmarking Simulation Study in Spain

What is The Economic Impact of CCP Test Misclassification in Rheumatoid Arthritis Diagnosis? A Benchmarking Simulation Study in Spain

Combination of “combinations of p values”

We investigate the impact of an uncertain number of false individual null hypotheses on commonly used p value combination methods. Under such uncertainty, these methods perform quite differently and often yield conflicting results. Consequently, we develop a combination of “combinations of p values” (CCP) test aimed at maintaining good power properties across such uncertainty. The CCP test is based on a simple union–intersection principle that exploits the weak correspondence between two underlying p value combination methods. Monte Carlo simulations show that the CCP test controls size and closely tracks the power of the best individual methods. We empirically apply the CCP test to explore the stationarity in real exchange rates and the information rigidity in inflation and output growth forecasts.

Determination of Specificity and Sensitivity of Rheumatoid Factor and Anti CCP Tests in Patients with RA in Private Clinic in Tehran, Iran

Introduction Rheumatoid Arthritis (RA) is a common systemic autoimmune disease that 1% of the world's population is suffering from it [1]. The disease, in addition to reducing the average life expectancy of patients, is associated with significant morbidity. So that 50% of RA patients are no

Rheumatoid Arthritis Serology in Macedonian Patients with Rheumatoid Arthritis: Rheumatoid Factor, Anti-Cyclic Citrulinated Peptide Antibodies or both?

Introduction : In the last 70 years, Rheumatoid Factor (RF) was considered the most useful laboratory marker in patients with rheumatoid arthritis (RA). The next very important milestone for the RA diagnosis was the discovery of anti-citrullinated peptide/protein antibodies (ACPA). The detection of ACPA is usually done with the CCP test of the second generation, CCP2. Objective : To evaluate the performances of RF and CCP2 tests and to see whether or not the performance of both tests together is better then the performances of either of the tests alone. Materials and Methods : We performed a cross-sectional study with 380 participants of which 155 RA patients who fulfilled the American College of Rheumatology (ACR) 1987 classification criteria for RA, 120 patients with inflammatory and other connective tissue diseases (Non-RA) and 105 healthy controls (HC), at the Rheumatology Clinic in Skopje, Macedonia. The patients and controls were tested for RF and ACPA. Results : The mean age of the RA patients was 50 years, and 87 % of the patients were female. The average duration of the disease has been 6 years. In this group of patients, CCP2 test showed identical sensitivity of 0,69 and better specificity than RF (0,95 vs. 0,87 respectively). For the patients who tested positive for both tests, the sensitivity was lower 0,60 and for the patients who were either ACPA or RF positive, sensitivity was slightly higher 0,73. The specificity of 0,88 for both or either of the tests was identical with that of RF. The positive likelihood ratio was 13,8 for the CCP2 test, 5,3 for RF and 5,1 for both tests done together. Ninety four out of 155 RA patients were positive for both ACPA and RF, 20 patients were positive for either one of the antibodies of which 7 (4,5%) RA patients were only anti-CCP positive and 13 (8,3%) patients were only RF positive. Conclusion : The results from our study showed that the sensitivity and specificity of both tests, done in parallel, does not differ much from the sensitivity of either of the tests alone and from the specificity of RF, respectfully. Still, CCP2 test showed the highest specificity and positive likelihood ratio as was expected. The results from our study support the idea that in countries like Macedonia, which can not afford enough CCP2 antibody kits, we may use RF first, especially in patients who are not likely to meet any clinical criteria for RA. In patients with early undifferentiated arthritis or early RA we may use both antibodies in order to select the patients who will need more aggressive treatment.

Impact of CCP test on personalizing treatment decisions: Results from a prospective registry of newly diagnosed prostate cancer patients.

Impact of CCP test on personalizing treatment decisions: Results from a prospective registry of newly diagnosed prostate cancer patients.

Anti-citrullinated peptide antibodies in Sudanese patients with Leishmania donovani infection exhibit reactivity not dependent on citrullination.

African patients with Leishmania donovani infections have signs of strong systemic inflammation and high levels of circulating immune complexes (IC) and rheumatoid factor (RF), all serologic markers of rheumatic disease. As inflammation in general is associated with citrullination, we sought to investigate ACPA responses in Sudanese Leishmania patients. Serum samples were collected from Sudanese patients with visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL) as well as from ACPA-positive Sudanese rheumatoid arthritis patients and compared to healthy Sudanese controls. Levels of circulating C1q-binding IC and anticyclic citrullinated peptide 2(CCP2) were investigated using ELISA, and RF was measured with nephelometry. C1q adsorption was carried out to investigate anti-CCP2 content in IC. Citrulline specificity was evaluated with control plates with cyclic arginine-containing control peptides. Leishmania-infected patients had elevated levels of RF and circulating IC but also a significant increase in anti-CCP2 (12%) as compared to healthy controls. Anti-CCP2-positive Leishmania patients displayed lower anti-CCP2 levels than Sudanese patients with rheumatoid arthritis (RA), and anti-CCP2 levels in Leishmania patients showed a continuum not resembling the dichotomous pattern seen in patients with RA. Whereas the anti-CCP reactivity of Sudanese RA sera was strictly citrulline dependent, anti-CCP2-positive Leishmania sera reacted equally well with ELISA plates containing arginine control peptides. There was a strong correlation between anti-CCP2 and circulating IC among the Leishmania patients, but IC depletion only marginally diminished anti-CCP2 levels. Our findings stress the importance to interpret a positive CCP test carefully when evaluated in non-rheumatic conditions associated with macrophage activation.

CCP score and risk stratification for prostate cancer patients at biopsy.

47 Background: New prognostic markers for prostate cancer play an important role in addressing the controversies of over diagnosis and treatment. The cell cycle progression score (CCP) (Prolaris, Myriad Genetic Laboratories, Inc.) is a new RNA-based marker, which improved the prediction of prostate cancer aggressiveness in eight separate cohorts. Each one-unit increase in CCP score corresponds with approximately a doubling of the risk of the studied event (recurrence or death from prostate cancer). In this analysis, we characterized the CCP score distribution from our initial CCP signature commercial testing. Methods: Our current laboratory database was evaluated for patients whose biopsy was analyzed with the CCP test and whose clinicopathologic data was collected by the ordering physician. Formalin fixed, prostate biopsy tissue from 1,648 patients diagnosed with adenocarcinoma ordered by more than 300 physicians were analyzed. The CCP score was calculated by measuring the RNA expression of 31 cell cycle progression genes normalized to 15 housekeeping genes. Results: Of the 1,648 samples that contained sufficient carcinoma (more than 0.5mm linear extent), 1,604 (97.3%) provided quality RNA for analysis. This retrospective analysis showed a normal distribution for the CCP score ranging from −2.9 to 3.1. Correlation with Gleason score was r=0.35. A relative classification of cancer aggressiveness based on CCP of approximately1,200 patients from multiple cohorts was developed to interpret how the patient’s CCP score compared to that of patients within the same AUA risk category. The thresholds between each of the five intervals are one unit of CCP score apart, with the "consistent" interval centered at the median CCP score. Based on the CCP score, 27.9% of men had a less aggressive cancer compared to the clinicopathologic prediction and were assigned to a lower risk group while 27.6% of patients had a more aggressive cancer. Conclusions: The CCP signature test is a novel assay that can improve risk stratification for men with prostate adenocarcinoma independent of the Gleason score and prostate-specific antigen level. Over 50% of men initially tested in the commercial assay were assigned to a different risk category than predicted by clinicopathologic features alone.

AB1259 Comparison of two assays for the determination of anti-citrullinated peptide antibodies (ACPA) using a routine patient cohort

BackgroundAnti-citrullinated peptide antibodies (ACPA) are an important serological marker in the diagnosis of rheumatoid arthritis (RA). A variety of different test systems are available for ACPA detection.ObjectivesThis study compares two...

Poor accuracy of anti-citrulline antibody test in diagnosis of rheumatoid arthritis in Iran

We read with interest the article on the utility of anti-CCP in Iran [1]. Although the authors have mentioned that ‘‘anti-CCP was measured by a second-generation ELISA,’’ the authors fail to provide the kit name or the cutoff value recommended by the kit. The study has defined ‘‘more than 15 U/ml as high titer,’’ which suggests they used the Euroimmun anti-CCP ELISA kit (Euroimmun AG, Luebeck, Germany) [2] which recommends a cutoff of 5 RU/ml. However, they mention the ELiA CCP test in the introduction, which recommends a cutoff of 10 U/ml [3]. It will be interesting to know the accuracy (sensitivity and specificity) when using kit-recommended cutoff apart from ‘‘high titer’’ cutoff used in this study. The authors found a sensitivity of anti-CCP to be 81 %, but found a specificity of only 77 %. This low specificity is of concern, being much lower than previously reported and claimed by manufacturers [2–5]. The authors have included 16 patients of ‘‘seronegative arthritis’’ (not defined in the text) out of 100 controls, making one wonder whether some of these were actually rheumatoid arthritis being picked up by the anti-CCP test. Interestingly, this study found rheumatoid factor to have a higher specificity (85 %) than antiCCP (77 %)! Finally, the authors have found 20 RU may be a more appropriate cutoff in their population. This is similar to other studies finding higher cutoffs than those recommended by manufacturers [6] and highlights the need to define population standards, rather than applying kit standards (based on different populations) indiscriminately.

Diagnostic utility of anti-cyclic citrullinated peptide antibodies in patients with early rheumatoid arthritis in the north of the country in Mexico. (159.18)

Abstract Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease which primarily causes a symmetric polyarthritis, which can progress into long-term disability. The diagnosis of RA combines the patient history of joint pain and stiffness, laboratory tests including biomarkers that can provide useful information to confirm the diagnosis of RA. To compare the diagnostic utility of biomarkers to confirm the diagnosis of RA, anticyclic citrullinated peptide (CCP) antibodies, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were tested in patients with early diagnosis RA. We work with 49 patients with RA all fulfilling the revised criteria of the ACR, and healthy volunteers. A commercial ELISA assay kit was used to test for anti-CCP antibodies; RF and CRP were measured by turbidimetric immunoassays; ESR was performed by Wintrobe assay. The levels of anti-CCP antibody titers, and FR were significantly higher in patients with early RA (54 % and 35% respectively) than in healthy controls (p <0.0001), however the 27% of patients were only positive to CCP test. No significant statistical correlation between anti-CCP antibody titers with inflammatory markers such as CRP or ESR was found. A positive predictive value was higher for anti-CCP antibodies in comparison to other markers.

Undrained cyclic triaxial behavior of saturated clays under variable confining pressure

A laboratory study on the undrained dynamic behavior of saturated clays in cyclic triaxial tests with a variable confining pressure (VCP tests) is presented. Tests were performed on remolded clayey samples using a dynamic triaxial device where the deviatoric stress and confining pressure can be varied simultaneously. Various cyclic stress paths have been applied on the specimens through varying the ratios or phase differences between the cyclic deviatoric stress and cyclic confining pressure. Specifically, the stress paths used in the present study were designed to simulate the coupling effects of simultaneously varying shear and normal stresses in clays due to earthquakes and other vibration sources. Test results obtained from this study show that the undrained response of saturated clays is strongly influenced by the variation of confining pressure, in terms of pore water pressure, development speed of cyclic strain and magnitude of cyclic strength. It is found that when strong P-waves are propagating in soil layers, VCP tests are more appropriate for the simulation of in situ stress fields than the conventional cyclic triaxial tests with a constant confining pressure (CCP tests).

Does testing for circulating autoantibodies against disease-relevant citrullinated antigens add value to the CCP2 assay in diagnosing RA among early undifferentiated arthritis patients?

BackgroundThe antigen substrates employed in the widely-used CCP2 assay do not correspond to in vivo-generated citrullinated proteins so far implicated in the potential pathogenesis of rheumatoid arthritis (RA). We assessed...

Comparison of the second and third generation anti-cyclic citrullinated peptide antibody assays in the diagnosis of Japanese patients with rheumatoid arthritis

The anti-cyclic citrullinated peptide (CCP) antibody has become increasingly important in the diagnosis of rheumatoid arthritis (RA), especially for early diagnosis. The purpose of this study is to compare the diagnostic usefulness of the second and third generation anti-CCP antibody kits among Japanese patients with RA. Anti-CCP antibody titers were measured with the second generation (MESACUP CCP test, Medical and biological laboratories) and third generation (QUANTA Lite CCP3 IgG ELISA, Inova Diagnostics) kits using serum samples from 106 rheumatoid arthritis (RA) patients and 57 non-RA patients. Sensitivities and specificities were compared. The sensitivity and specificity of the second generation anti-CCP (anti-CCP2) kit were 88.7 and 89.5%, and those of the third generation anti-CCP (anti-CCP3) kit were 91.5 and 87.7%. Area under the receiver operating curve showed that anti-CCP2 and anti-CCP3 had similar diagnostic performances. Diagnostic performance of the anti-CCP3 assay was comparable with the anti-CCP2 assay in Japanese patients with RA.

Autoantibodies and the Risk of Cardiovascular Events

Inflammation and autoimmunity are associated with increased cardiovascular (CV) risk in patients with rheumatoid arthritis. This association may also be present in those without rheumatic diseases. Our purpose was to determine whether rheumatoid factor (RF), antinuclear antibody (ANA), and cyclic citrullinated peptide antibody (CCP) positivity are associated with increased risk of CV events and overall mortality in those with and without rheumatic diseases. We performed a population-based cohort study of all subjects who had a RF and/or ANA test performed between January 1, 1990, and January 1, 2000, and/or CCP test performed between September 1, 2003, and January 1, 2005, with followup until April 1, 2007. Outcomes were ascertained using diagnostic indices from complete medical records, including CV events [myocardial infarction (MI), heart failure (HF), and peripheral vascular disease (PVD)] and mortality. Cox models were used to analyze the data. There were 6783 subjects with RF, 7852 with ANA, and 299 with CCP testing. Of these, 10.4%, 23.9%, and 14.7% were positive for RF, ANA, and CCP, respectively. Adjusting for age, sex, calendar year, comorbidity, and rheumatic disease, RF and ANA positivity were significant predictors of CV events [hazard ratio (HR) 1.24 and 1.26] and death (HR 1.43 and 1.18). Adjusting for age, CCP positivity was associated with CV events, but this association was not statistically significant (HR 3.1; 95% CI 0.8, 12.3). RF and ANA positivity are significant predictors of CV events and mortality in both those with and those without rheumatic diseases. These results support the role of immune dysregulation in the etiology of CV disease.

Antibodies to citrullinated peptides: a significant step forward in the early diagnosis of rheumatoid arthritis

The early diagnosis of rheumatoid arthritis (RA) has become a priority owing to the availability of effective disease-modifying agents that can improve patient wellbeing and influence the clinical outcome. However, this represents a real challenge, as no clinical, radiological or immunological features are pathognomonic at the time of presentation. For this reason, development of the anti-cyclic citrullinated peptide (CCP) antibody assay, a highly disease-specific serological marker for RA, has been a great step forward for the rheumatologist and the clinical laboratory. Over recent years, this test has increased in popularity and many studies have been performed. This review briefly considers the most recent data on the diagnostic accuracy of the CCP test, the genetic background that predisposes to antibody production, the diagnostic, prognostic and predictive values, and the clinical use of the assay in patients with RA.

Association of Anti‐Cyclic Citrullinated Peptide Antibodies, Anti‐Citrullin Antibodies, and IgM and IgA Rheumatoid Factors with Serological Parameters of Disease Activity in Rheumatoid Arthritis

We evaluated the association of anti-cyclic citrullinated peptide (CCP) antibody titers with serological markers of disease activity. We also compared three different anti-CCP antibody ELISAs with an anti-citrullin ELISA and the IgM and the IgA rheumatoid factor (RF) in their performance of discriminating between rheumatoid arthritis (RA) and other rheumatic diseases. Sera from 333 consecutive patients of the Rheumaeinheit der Medizinischen Poliklinik Munchen, an outpatient clinic for rheumatic diseases, were collected and tested. Anti-CCP antibodies were assayed with three different commercially available ELISAs. Antifilaggrin antibodies were tested with a commercially available ELISA using in vitro deiminated recombinant rat filaggrin. IgA-RF was analyzed with an ELISA, whereas IgM-RF was measured by latex-enhanced turbidimetry. Rheumatoid arthritis (RA) was diagnosed in 87 patients according to the revised classification criteria of the American College of Rheumatology (ACR), probable RA was diagnosed in 23 patients in an early phase not (yet) fulfilling the ACR criteria, and 223 patients had other rheumatic diseases. Differences in sensitivity and specificity were calculated using McNemar's test. A measure of agreement (kappa statistic) was used to examine whether the tests tended to identify the same patients as positive or negative. Correlations between CCP titers and other tests were analyzed by Spearman nonparametric rank correlation. No significant differences in sensitivity and specificity were found between the tested CCP assays (80.0-80.9% and 97.3-98.1%, respectively). All three CCP tests were slightly but not significantly more sensitive and specific than the anti-citrullin assay (77% and 92%, respectively), comparably sensitive but significantly more specific compared with the IgM-RF (86% and 82%, respectively), and significantly more sensitive but comparably specific compared with the IgA-RF (63% and 94.4%, respectively) in detecting the patients with RA. There was no significant correlation between anti-CCP, anti-citrullin, or IgM-RF or IgA-RF antibody titers and C-reactive protein, erythrocyte sedimentation rate, or white blood cell count. A weak but significant linear correlation was found between anti-CCP titers and IgM-RF titers (r = 0.2, P = 0.03). We could not find a significant difference between the three tested anti-CCP assays and the anti-citrullin test in terms of sensitivity and specificity. Compared with the IgM-RF, all the anti-CCP assays were superior in specificity and comparable in sensitivity. Compared with the IgA-RF, they were more sensitive and comparably specific in the discrimination of patients with RA from other rheumatic diseases. No correlation of any tested autoantibody titer with serological parameters of inflammation was found.

Ciliocytophthoria (ccp) in nasopharyngeal smear from patients with acute tonsillitis.

Ciliocytophthoria (ccp) in nasal or nasopharyngeal secretion from the patients with acute tonsillitis, acute rhinosinusitis and allergic rhinitis was studied. The ratio of the presence of ccp among acute tonsillitis, acute rhinosinusitis and allergic rhinitis was compared. Acute tonsillitis had a much more positive ccp test than other diseases. This might be related to the anatomical feature of palatine tonsil having a complicated hollow-crypt. The presence of Haemophilus influenzae was the most frequent in patients with positive ccp test. Further study will be necessary to determine possible relationship between viral infection and bacteria or endotoxin from bacteria.