Cold Agglutinin Test Research Articles

Efficacy of sutimlimab for cold agglutinin disease in a patient on chronic hemodialysis.

Reports of cold agglutinin disease (CAD), an autoimmune hemolytic anemia, in dialysis patients are limited. Recently, sutimlimab for CAD was covered by insurance. Herein, we report a case in which sutimlimab was effective in the treatment of CAD in a patient undergoing hemodialysis (HD). The patient was a 73year-old Japanese man with an 11year history of HD for diabetic nephropathy. He was admitted to our hospital for examination and treatment of erythropoiesis-stimulating agent (ESA)-induced hyporesponsive anemia and fatigue, which was present in the previous year October to March when temperatures were cooler. The patient was diagnosed with hemolytic anemia based on decreased hemoglobin levels, elevated reticulocyte count, elevated lactate dehydrogenase levels, and decreased haptoglobin levels. Furthermore, he was diagnosed with CAD based on a positive direct antiglobulin test for C3 and cold agglutinin tests. The patient did not respond well to an elevated dialysate temperature or rituximab therapy. After initiating sutimlimab treatment, an increase in the hemoglobin level was observed despite a decrease in temperature, and his fatigue disappeared. Anemia in hemodialysis patients is generally renal; however, some ESA resistance exists, which may be due to hemolytic anemia. In this case, the use of sutimlimab was effective in controlling hemolytic anemia due to CAD.

Cryoglobulins and cold agglutinins for hand arm vibration syndrome.

Hand arm vibration syndrome (HAVS) is a condition caused by hand transmitted vibration from the use of hand-held vibrating tools or workpieces. The disease affects the vascular, neurological and musculoskeletal systems. The vascular component of HAVS is a form of secondary Raynaud's phenomenon. Other causes of disease must be excluded before attributing the cause to hand transmitted vibration. To evaluate the prevalence, and utility of testing for, cryoglobulins and cold agglutinins in patients with HAVS symptoms. A retrospective cohort study of 1183 patients referred for HAVS clinical assessment at St. Michael's Hospital, Toronto, Canada, between 2014 and 2020. The standard operating procedure at the clinic includes a detailed clinical and exposure history, physical examination, objective investigations and blood tests. Data were retrieved from patient chart review and laboratory investigation results for all cases with cryoglobulin and cold agglutinin testing. A total of 1183 patients had a serum cryoglobulin measurement. Eleven patients (1%) were positive. Seven positive results were 'low titre' (1% positive) and the other four results were 2%, 6%, 9% and 18%. The patient with a 9% positive cryoglobulin titre had previously diagnosed Sjögren's syndrome. There were no positive cold agglutinin tests in the 795 patients tested. Routine testing for cryoglobulins and cold agglutinins in patients with HAVS symptoms is not recommended because test positivity rates are negligible. Testing may be considered if the clinical history or routine blood investigations suggest evidence of underlying cryoglobulinaemia or cold agglutinin disease.

Cold Agglutinins and Cryoglobulins Associate With Clinical and Laboratory Parameters of Cold Urticaria.

Mast cell-activating signals in cold urticaria are not yet well defined and are likely to be heterogeneous. Cold agglutinins and cryoglobulins have been described as factors possibly associated with cold urticaria, but their relevance has not been explained. We performed a single-center prospective cohort study of 35 cold urticaria patients. Cold agglutinin and cryoglobulin test results, demographics, detailed history data, cold stimulation test results, complete blood count values, C-reactive protein, total immunoglobulin E levels, and basal serum tryptase levels were analyzed. Forty six percent (n = 16) of 35 tested patients had a positive cold agglutinin test and 27% (n = 9) of 33 tested patients had a positive cryoglobulin test. Cold agglutinin positive patients, when compared to cold agglutinin negative ones, were mainly female (P = 0.030). No gender-association was found for cryoglobulins. A positive cold agglutinin test, but not a positive cryoglobulin test, was associated with a higher rate of reactions triggered by cold ambient air (P = 0.009) or immersion in cold water (P = 0.041), and aggravated by increased summer humidity (P = 0.007). Additionally, patients with a positive cold agglutinin test had a higher frequency of angioedema triggered by ingestion of cold foods or drinks (P = 0.043), and lower disease control based on Urticaria Control Test (P = 0.023). Cold agglutinin levels correlated with erythrocyte counts (r = −0.372, P = 0.028) and monocyte counts (r = −0.425, P = 0.011). Cryoglobulin concentrations correlated with basal serum tryptase levels (r = 0.733, P = 0.025) and cold urticaria duration (r = 0.683, P = 0.042). Results of our study suggest that cold agglutinins and cryoglobulins, in a subpopulation of cold urticaria patients, are linked to the course and possibly the pathogenesis of their disease.

Mycoplasma pneumonia among children with acute respiratory infection

Background: Acute respiratory infection (ARI) is one of the leading causes of mortality and morbidity in children. Mycoplasma pneumonia remains the most common species causing ARI in school going children. IgM ELISA is considered as the single most appropriate test for diagnosis of acute mycoplasma pneumonia infection. Objectives of the study was to assess the proportion of mycoplasma pneumonia among children aged 2-12 years admitted with ARI using IgM ELISA kit.Methods: Study design included prospective descriptive study. Study carried out at Amala institute of medical sciences, Thrissur, Kerala, India. Study period from January 2019 to June 2020. Inclusion criteria included all children between age group 2-12 years admitted in paediatrics department with clinical features of ARI. Exclusion criteria excluded parents/patients who are not willing to participate in the study and patients who are known cases of reactive airway disease. A total of 124 children, aged 2-12 years with clinical features of ARI admitted during January 2019 to June 2020 were included in this study. This was to know the proportion of Mycoplasma pneumonia among these children using IgM ELISA test kit and to understand their clinical profile.Results: 71 were males. Mean age of children in the study group was 4.4±2.4. IgM ELISA was positive in 9 subjects (7.3%). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 50, 85, 40, 89.7 and 79.5% respectively.Conclusions: Prevalence of Mycoplasma pneumonia in our population based on IgM ELISA was 7.3%. Mycoplasma pneumonia IgM ELISA test is superior to cold agglutinin test.

Features of serum complement C3 and C4 levels in autoimmune hemolytic anemia patients.

Abnormally activated complement system induces erythrolysis in a part of autoimmune hemolytic anemia (AIHA) patients. However, the alterations in serum complement levels in these patients are seldom reported. In this study, we aimed to evaluate the serum complement features of AIHA patients according to different clinical and laboratory characteristics and to find relationships between complement levels and hemolysis-associated laboratory indexes. A retrospective analysis of 146 AIHA patients was performed, and serum complement C3 and C4 levels were compared between control subjects and AIHA patients with different subtypes. Correlations of serum C3/C4 levels with titers of cold agglutinin test (CAT), direct antiglobulin test (DAT), and serological indexes were assessed. Spearman correlation analysis was performed to analyze the relationship between serum complement levels and other laboratory indexes. Autoimmune hemolytic anemia patients showed reduced serum C3 levels, while serum C4 levels tended to be lower in DAT-positive AIHA patients but not in DAT-negative AIHA patients. Patients with warm AIHA secondary to connective tissue diseases and cold agglutinin disease/cold agglutinin syndrome had the lowest serum C3/C4 levels. Serum C4 levels were negatively correlated with CAT (P=.004) and DAT (anti-C3d) (P=.007) titers. In patients with positive CAT and/or DAT (anti-C3d) but negative DAT (anti-IgG), serum C3/C4 levels were negatively correlated with indirect bilirubin (P=.017 and =.026, respectively). The study findings may be helpful in not only unraveling the mechanism underlying hemolysis in AIHA but also diagnosing AIHA and selecting targeted treatment strategies.

Reliability of cold agglutinin test (CAT) for the detection of patients with Mycoplasma pneumoniae pneumonia

Introduction : M. pneumoniae is one of the causative agents of primary atypical pneumonia. This infection causes 20-40% of community acquired pneumonia and is associated with an array of extra-pulmonary manifestations. There is a need for a rapid diagnostic test in order to prescribe prompt and appropriate antibiotic therapy. Even though isotype specific antibody testing provides definitive diagnosis, paired sera testing does not help in real time diagnosis. Cold agglutinins detectable by the Cold Agglutination Test (CAT) appear and disappear early in infection compared to long lasting specific antibodies that are detectable by specific immunoassays. Although there are some reports suggesting CAT is unreliable, it is being often used to diagnose M. pneumoniae pneumonia in Sri Lankan clinical settings. The aim of the current study was to evaluate the use of CAT as a bed-side screening test for early diagnosis of M. pneumoniae pneumonia compared to ELISA for detection of specific antibodies in the Sri Lankan context. Methods: Ninety seven clinically and radiologically confirmed patients with pneumonia were enrolled in the study. CAT was performed on acute stage sera. A CAT titer ≥1/32 was considered as positive. Isotype specific M. pneumoniae ELISA with paired sera was compared with CAT results. Results: Mycoplasma pneumonia was confirmed in 15 of the 97 patients in the study using Mycoplasma specific IgM and 4 fold rise in titre. Of these, 3 were positive by the CAT. The sensitivity and specificity of the CAT compared to IgM/4fold rise in IgG detection were 20% (3/15) and 81.7% (67/82) respectively. Negative and positive predictive values of the CAT compared to ELISA were 84.8% (67/79) and 16.7% (3/18) respectively. Conclusion: CAT is not a reliable screening test compared to specific antibody detection by isotype ELISA for the detection of M. pneumoniae pneumonia due to its low sensitivity and positive predictive values.

A Case of Cold Agglutinin Disease Associated with Mycoplasma Pneumonia

A 19-year-old male patient was admitted to the hospital with a fever and cough. His chest X-ray showed right lower lobe infiltration consistent with the diagnosis of pneumonia. On the fifth day after admission, he started complaining about dark urine and jaundice, and his hemoglobin level dropped from 14 g/dl to 8 g/dl, with up regulation of unconjugated bilirubin. The nurses noticed clotting of his blood immediately after they drew the blood. A blood smear without magnification on the left side in Figure 1 (panel A) is the control; the patient’s blood smear (panel B) showed clumps before staining. Warming to 37°C at room temperature caused his blood to undergo agglutination (Figure 2, arrow). Results of a cold-agglutinin test were strongly positive (anti-I). Serological testing for mycoplasma showed a high titer of anti-mycoplasma IgM (without IgG). The patient was treated with levofloxacin and showed an excellent response; his cold agglutinin disease resolved. As seen in the current patient, potent cold agglutinins can cause specific problems, especially when reactivity persists at temperatures above room temperature. The acute form of cold agglutinin disease is often secondary to mycoplasma infection or lymphoproliferative disorders

Cold agglutinin disease associated with mycoplasma infection in an individual with type 2 diabetes: An atypical case

Cold Agglutinin Disease is a hemolytic anemia associated with cold reactive autoantibodies. Although the acute form of cold agglutinin disease can be attributed to autoimmune or infectious diseases and lymphoproliferative diseases, it has, to the best of our knowledge, so far，never been reported as secondary to mycoplasma pneumonia in a type 2 diabetic individual. In this paper, we report a case of cold agglutinin disease following mycoplasma pneumonia in a 47-year-old female patient with type 2 diabetes and schizophrenia. Cold agglutinin test and direct Coombs’ test was positive. Anti-mycoplasma anti-body titre by complement fixation was high (Anti-IgG was negative and Anti-C3d was positive) and was accompanied by hemolytic anemia. Her general condition, including Cold Agglutinin Disease improved after conservative therapy with antibiotics, hypoglycemic agents and short-term use of steroids. The patient recuperated and was discharged in good health after 7 days’ stay in the hospital. She remains clinically well with no recurrence of anemia. The simultaneous occurrence of cold agglutinin disease, mycoplasma infection and diabetes mellitus is rare and accumulation of case reports is required to gain better insight of this case scenario.

Cold agglutinin disease in fibrolamellar hepatocellular carcinoma: a rare association with a rare cancer variant

Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia. Although it can occur secondary to lymphoproliferative disorders and autoimmune or infectious diseases, CAD is rarely reported as secondary to solid tumors. We report a case of a woman aged 18 years diagnosed with a well-differentiated hepatocellular carcinoma of the fibrolamellar subtype, who was shown to have CAD also. Her general condition, including CAD, improved after targeted therapy with sorafenib for the hepatocellular carcinoma and only conservative measures for the CAD that consisted of avoidance of cold. In summary, although it is an extremely rare association and less common than lymphoproliferative disorders, CAD can be associated with solid tumors.

Reação leucemoide e anemia hemolítica grave causada por Mycoplasma pneumoniae

Hemólise massiva é uma manifestação rara da infecção por Mycoplasma pneumoniae.É desencadeada por crioaglutininas, anticorpos IgM, que surgem sete a dez dias após a infecção em cerca de 50% a 75% dos casos. Hiperleucocitose é também evento incomum e orienta o diagnóstico para etiologia bacteriana ou neoplásica. Relatamos um caso de um homem de 67 anos com pneumonia por Mycoplasma pneumoniae, que apresentou anemia grave e reação leucemoide, diagnosticada por meio do teste de crioaglutininas à beira do leito e dosagem do título de anticorpo anti-mycoplasma. Após início do tratamento adequado, houve melhora importante da anemia e a leucometria foi reduzida de 56.100/mm³ para valores próximos do normal.

Enzyme immunoassay for detection of immunoglobulin M (IgM) and IgG antibodies to Mycoplasma pneumoniae.

An enzyme immunoassay (EIA) for detection of immunoglobulin M (IgM) and IgG antibodies to Mycoplasma pneumoniae was developed. The EIA was evaluated on the basis of results in the M. pneumoniae complement fixation (MPCF) test and the cold agglutinin test. Serum samples from 430 patients with respiratory infections of known or unknown etiology, from 91 healthy children and adults and from 20 patients with rheumatoid factor, were investigated. By the criteria chosen for positive diagnostic EIA values, we found that the combined measurement of specific IgM and IgG gave a specificity of 99.7% and a sensitivity of 97.8%. If only IgM antibodies were measured, the specificity was 100% and the sensitivity was 88%. For IgG alone the specificity was 99.7%, but the sensitivity was only 46% because of the high EIA cutoff value chosen for IgG. We found no false positives among serum samples from patients with non-M. pneumoniae respiratory infection of known etiology, and there were no false IgM positives due to rheumatoid factor. In some cases the IgM EIA results became positive earlier in the course of illness than the MPCF titer. While children and teenagers responded predominantly with IgM antibodies, patients older than 40 years often had an IgG response only (56% of cases), probably because of reinfection. We conclude that this EIA is a good alternative to the combined MPCF and cold agglutinin tests in the diagnosis of M. pneumoniae infection.

A case of mycoplasma pneumonia complicated with acute respiratory failure.

Mycoplasma pneumoniae produces illness in man ranging from mild upper respiratory tract infection to severe bronchitis and pneumonia. We experienced a case of mycoplasma pneumonia complicated with acute respiratory failure, cold agglutinin hemolytic anemia, pleural effusion, Raynaud's phenominon and hepatitis in 27-year-old female. She was diagnosed as having mycoplasma pneumonia by detecting mycoplasma antibody and cold agglutinin test and treated effectively with erythromycin.

IMMUNOLOGICAL ASPECTS OF MYCOPLASMA PNEUNONIAE INFECTION FROM A VIEW POINT OF ANTIBODY RESPONSES (2 ND REPORT)

Radioallergosorbent test (RAST) was performed for the measurement of anti-Mycoplasma pneumoniae (Mp) IgG, IgD, IgE and complement fixing (CF) antibodies and cold agglutinin (CA) in the sera of 25 patients with primary atypical pneumonia (PAP) and controls. Of infants three years old or younger, 11% were positive for CF antibody, whereas positive rates for IgD, IgG and IgE antibody to Mp were 100%, 44% and 12.5%, respectively. The positive rates for IgD and IgG antibody to Mp were higher than that of CF antibody. Levels of IgE antibody in patients with high CA titers were significantly higher than those in patients with low CA titers.In conclusion, measurement of IgD and IgG antibody to Mp was useful in the serological diagnosis of infant Mp pneumonias. IgE antibody to Mp with cold agglutinin test would also support diagnosis in the cases with low CF titers.

Epidemic pneumonia in university students

Longitudinal surveillance of pneumonia in a univeisity student health service was conducted from 1965–1971 and 1984–1987. Of 104 pneumonia cases documented by chest x-ray, only six were presumed to have bacterial etiology; the remaining 98 were characteristic of atypical pneumonia syndrome. Mycoplasma pneumoniae was the etiology in 51% of the pneumonias in the 1960s and 13% in 1984–1987. Pneumonia incidence was highest in the fall semester in seven of 11 years studied. Annual incidence followed a three- to four-year periodicity. Both of these observations mirror the epidemiology of M. pneumoniae in the world population. Symptoms of cough, headache, malaise, and absence of the physical finding of wheezing were seen more consistently in M. pneumoniae pneumonia than in other atypical pneumonias; other clinical features varied among epidemics. Rapid cold agglutinin tests were positive in 27% of our clinically diagnosed pneumonias and in 36% of those with documented mycoplasmal infections. This study appears to provide a basis for predicting future epidemics of atypical pneumonia in student populations.

Rapid Noninvasive Techniques for Determining Etiology of Bronchitis and Pneumonia in Infants and Children

Table 2 lists the names, abbreviations, and principle underlying most of the rapid diagnostic techniques we have described. Table 3 lists the pathogens most likely to cause lower respiratory tract infections in pediatric patients, the specimens needed for each rapid diagnostic test now generally available, and the approximate time required for its actual performance. For maximal cost-effectiveness, it is recommended that laboratory diagnosis be pursued in a stepwise manner: 1) The usual patient with acute respiratory illness who is to be managed as an outpatient may need little if any laboratory evaluation. 2) For the child for whom hospital admission is being considered, serum C-reactive protein screen, urine bacterial antigen tests, and a cold agglutinin test (at the appropriate age) will help to classify the etiology of the infection as likely or unlikely to be bacterial. If antibiotic therapy is to be given, a blood culture should be obtained before starting. 3) For the child admitted to the hospital with a possible chlamydial or viral lower respiratory infection for whom specific therapy is considered, nasopharyngeal secretions should be examined for Chlamydia and for antigens of respiratory syncytial, parainfluenza, and influenza viruses to help select the appropriate antimicrobial. Serum for IgM level may be helpful. 4) For the child who has been intubated for respiratory support, a specimen of deep respiratory secretions should be sent for Gram stain, bacterial culture, for Chlamydia, and viral antigens and culture. 5) For patients presenting with atypical symptoms, signs, or clinical course additional diagnostic possibilities should be considered and appropriate tests done even if results may not be available within 48 hours.

Diagnostic Significance of Cold Agglutinin and Antimycoplasma Antibody for Mycoplasma pneumoniae Infection

A study to evaluate the diagnostic significance of M. pneumoniae Infection by measurements of cold agglutinin and antimycoplasma antibody titers is performed with 191 pediatric patients who have visited Yeungnam University Hospital during the period through January to July, 1987. Forty eight of 191 cases made follow up tests feasible. The results obtained are as follows: 1. It is necessary to perform routine combined measurements of cold agglutinin and antimycoplasma antibody titers for the all pediatric pneumonia caser since a large proportion of pneumonia in children is caused by M. pneumonia. 2. For the diagnosis of M. pneumoniae Infection, measurements of cold agglutinin titer alone seems to be less significant than to check both cold agglutinin and antimycoplasma antibody titers. 3. The measurement of antimycoplasma antibody titer appeared to be more specific than cold agglutinin test in the diagnosis of M. pneumoniae Infection. 4. The present study urges the necessity of follow up study of cold agglutinin and antimycoplasma antibody titer for those who initially presented with normal titers in both tests, but are clinically suspected for M. pneumoniae Infection.

An aid to the rapid diagnosis of Mycoplasma pneumoniae infections.

Although Mycoplasma pneumoniae has been isolated with fairly high frequency from the throats of patients infected with this agent [1-3], the patient is often discharged from the hospital before definitive results can be obtained. The cold agglutinin test [4; 5, p. 51] is widely used as a means of serologic diagnosis; however, cold agglutinins are not specific [6], and titers of less than 1:64 are generally considered inconclusive. In other serologic tests, such as complement fixation (CF) [7], hemagglutination inhibition (HI) [8], and tetrazolium reduction inhibition (TRI) [9], it has been necessary to demonstrate a significant rise in antibody titer between paired specimens of serum. The present method makes it possible, by the demonstration of early 19S CF antibody sensitive to 2-mercapto-ethanol (2-ME), to confirm the diagnosis using a single specimen of serum and to obtain the results within 1-2 days after the blood is drawn.

Laboratory Diagnosis of Mycoplasma Pneumoniae Infection

In man M. pneumoniae most often causes a primary atypical pneumonia. The serum of many patients so afflicted will quickly show positive cold agglutinin and complement-fixation tests. Although nonspecific, these tests are rapid. Laboratories can also culture organisms from throat swabs and sputum in special mediums, but growth takes at least seven days and sometimes six weeks.

Bullous Myringitis and Atypical Pneumonia

To the Editor:— I read with interest the recent letter of T. J. John, MD, et al ( 201 :273, 1967) concerning the association of bullous myringitis and primary atypical pneumonia. I recently published a study in which we attempted to relate the incidence of bullous myringitis with the Eaton agent, Mycoplasma pneumoniae . In 23 cases of bullous myringitis, complement fixation tests, viral isolation techniques, throat cultures, cold and MG agglutinin tests failed to establish a causal relationship. Complement fixation tests against 21 common viral agents also failed to indicate a relationship. It is my current thought that bullous lesions are probably nonspecific manifestations of mechanical injury which may be associated with upper-respiratory tract infection. I have also been impressed with the frequent occurrence of this disease in children afflicted with allergic diseases.

PNEUMONIA AND INLTAL DIAGNOSlS OF MINIMAL PULMONARY TUBERCULOSIS

From October 1964 to September 1965 for one year the author experienced 8 cases of transient pneumonia like X-ray shadows out of 1,000 cases of USA visa medical examination. These cases were at first diagnosed as minimal pulmonary tuberculosis but had to change the diagnosis as pneumonia after one to two weeks or 3 weeks because of complete disappearance of the precious shadows. The exact nature of these shadows could not be definitely determined. However 6 cases stated that they had a cold for several days and all of hose cases showed no tuberculosis bacilli in sputum on examinations of throat swab smear and culture. Cold agglutinin test was done on only 2 cases and it were also negative. The relationship with influenza also was not directly conformable. Although the incidence of these pneumonia was only 0.8% of total 1,000 examinee, when compared with the fact that there were only 4 cases whom were de initely diagnosed as minimal pulmonary tuberculosis the frequency rate of pneumonia against initial minimal pulmonary tuberculosis would be 2 to 1 in this visa medical examination. From this experience the author emphasized that before the initial diagnosis of minimal pulmonary tuberculosis is made in these sort of physical examination, should have another chest X-ray after 2 to 3 weeks of the first chest X-ray to differentiate the transient pneumonic shadow from tuberculosis. The size and the location of the shadows were various and there was no distinguishable point on X-ray picture between these pneumonic cases and tuberculosis.