Cold Agglutinin Titer Research Articles

WARM AUTOIMMUNE HEMOLYTIC ANEMIA FOLLOWING RECURRENT MYCOPLASMA PNEUMONIA INFECTIONS IN A CHILD WITH DOWN SYNDROME

Mycoplasma pneumonia (MP) is mainly associated with cold agglutinin syndrome, whereas both cold IgM and warm IgG autoantibodies have been identified in only two cases in the literature. The authors present an 8-year-old boy with Down syndrome, who suffered from recurrent episodes of MP infection, followed by episodes of hemolytic anemia with normal titer of cold agglutinins. The first 6 episodes were sequenced by nonimmune hemolytic anemia, whereas the latter 7 episodes were followed by episodes of warm autoimmune hemolytic anemia. This is believed to be the first described case of hemolytic anemia with warm IgG autoantibodies, following MP infection.

Severe cold agglutinin disease caused by recurrent monomorphic Epstein–Barr virus (EBV)‐associated post‐transplant lymphoproliferative disorder (PTLD), clonally related to an EBV‐negative plasmacytic hyperplasia in a pediatric multivisceral organ transplant recipient

PTLD represent major post-transplant complications. The major etiologic factor is EBV. Association with cold agglutinin disease has not been described so far. We report a three-yr-old girl who developed oligoclonal EBV-negative plasmacytic hyperplasia as well as Coombs test-positive anemia one yr after multivisceral organ transplantation, performed after subtotal bowel resection for colointestinal aganglionosis and liver cirrhosis resulting from long-term parenteral nutrition. The patient was treated for plasmacytic hyperplasia with cyclophosphamide and prednisolone and achieved clinical remission. One yr later PTLD progressed possibly driven by EBV to DLBCL. The migration patterns of the amplified Ig heavy chain genes demonstrated a probable clonal relationship of the DLBCL to a clone almost present in the plasmacytic hyperplasia. This progression was accompanied by a rapid rise of cold agglutinin titers with symptoms of severe cold agglutinin disease, leading to right femoral and extern iliac vein thromboses requiring partial leg amputation. After four cycles of rituximab, cyclophosphamide, and prednisolone, the patient achieved complete PTLD remission and the cold agglutinins disappeared. Summarizing, PTLD may be accompanied by cold agglutinin disease, and both may be successfully treated by immuno-chemotherapy. The appearance of cold agglutinins in transplant patients may indicate PTLD development.

Mycoplasma pneumoniae Associated with Hemolytic Anemia, Cold Agglutinins, and Recurrent Arterial Thrombosis

A 40-year-old white male developed Mycoplasma pneumoniae pneumonia (IgM titer 1:256) as well as autoimmune hemolytic anemia due to cold agglutinins (titer of 1:512). Four days after admission to the hospital, he developed an acute superior mesenteric artery (SMA) thrombosis. Four feet of ischemic small bowel were resected. A follow-up angiogram again showed SMA thrombosis and a left popliteal artery thrombosis. The patient was returned to the operating room and underwent thrombectomy of the affected arteries. The following day, he again developed a left popliteal artery thrombosis requiring thrombectomy. Plasmapheresis, Coumadin and prednisone were implemented. No further thrombotic events occurred. Hypercoagulability workup was negative. Pathology samples revealed vasculitis. Based on a negative hypercoagulability workup, nonrecurrence of thrombotic events after treatment, and in the absence of any structural abnormalities of the affected arteries, an autoimmune phenomenon with damage to the endothelium was thought to have played a role in the mechanism of thrombosis.

Cold Agglutinin Syndrome in Post-Liver Transplant Patients on Tacrolimus.

Following liver transplantation, patients require immunosuppressive medications to prevent graft rejection. However, these drugs can have significant side effects including severe anemia. Tacrolimus is now commonly used in pediatrics patients after liver transplantation. Case reports indicate that tacrolimus rarely can cause microangiopathic hemolytic anemia and also hemolytic anemia due to cold reactive IgM antibodies (cold agglutinin disease). We have seen 4 patients with symptomatic cold agglutinins thought to have been triggered by tacrolimus. Four patients, 6 to 26 months post-ABO-compatible liver transplant, presented with severe anemia (hemoglobin < 6g/dL), indirect hyperbilirubinemia, reticulocytosis and low serum haptoglobin (Table 1). Peripheral blood smear exhibited marked autoagglutination but no evidence of microangiopathic changes. The direct antiglobulin test (DAT) initially was strongly positive in all 4 patients (Table 2). After warm saline washes, the DAT remained positive for complements in 3 out of 4 patients. Cold agglutinin titers were low (1:4 – 1:16) but thermal amplitude studies were positive at 37°C in the two tested patients. Viral serologies significant for cold agglutinin syndrome were negative. None of the patients had clinical evidence of post-transplant lymphoproliferative disorder. All 4 patients had brisk hemolysis requiring multiple uncrossmatched packed red blood cells (PRBC) transfusions. Favorable resolution of the hemolytic anemia occurred following steroids, plasmapheresis and withdrawal of tacrolimus. Subsequently, patients were placed on cyclosporin and none exhibited liver rejection or recurrence of their hemolytic anemia. The above observation indicates that acute cold-agglutinin induced hemolysis occurs in patients following liver transplantation and these events appear to have temporally associated with tacrolimus administration.Patient ProfilesPatientAgeDiagnosisMonths after transplantPresenting hemoglobin (g/dL)Reticulocyte (%/Abs k/μLTotal/Direct BilirubinTreatments (in addition to withdrawal of tacrolimus)18 mosNeonatal iron storage disease62.841%/4694.2/0.6MP 4mg/kg/d plus 30mg/kg/d x 3 days. Plasmapheresis x 6.213 mosBiliary atresia Idiopathic65.38%/2503.2/0.4MP 4mg/kg/d. Plasmapheresis x 15.32 yrs 5 mosfulminant hepatic failure144.619.5%/2372.6/0.3MP 10mg/kg/d. Plasmapheresis x 10.44 yrsBiliary atresia265.35%/ND8.8/0.5MP 2mg/kg/d→ 4mg/kg/d. Plasmapheresis x 10.ND=not done. MP=methylprednisoloneImmunohematology ProfilesAdmission DATPatient 1Patient 2Patient 3Patient 4Admission DATPre/post saline washPre/post saline washPre/post saline washPre/post saline washPolyspecific3+/01+/M+4+/4+3+/1+Anti-IgG2+/0M+/04+/1+3+/1+Anti-C32+/02+/1+4+/4+3+/1+Saline Control2+/01+/01+/01+/0Eluate0NTPanreactive 1+Panreactive 1+Cold agglutinin titer at 4°C in salineNT4816Thermal amplitude screen at 30°CNTNTReactiveReactiveDonath-Landsteiner TestNTNTNegativeNegativeAdmission peripheral blood smear4+ polychromatophilia. 4+ microcytosis4+ autoagglutination. 3+ polychromatophilia. 3+ spherocytes. 3+ microcytes3+ autoagglutination. 3+ polychromatophilia. 3+ spherocytes. 2+ macrocytes4+ autoagglutination. 4+ spherocytes. 2+ polychromatophilia. 2+ macrocytesDAT-Direct antiglobulin test, M-microscopically, NT-not tested, +-positive, 0-negative,

Influence of clinical factors on the haemolysis marker haptoglobin

Plasma haptoglobin determination is clinically used as parameter for haemolysis. To date, however, the influence of the mode of haemolysis (extravascular vs. intravascular) and of nonhaemolytic conditions on haptoglobin concentration and its reliability as a haemolysis marker remain poorly defined. In a total of 479 individuals, the influence of haemolytic and nonhaemolytic conditions on plasma haptoglobin levels was investigated. All studied types of haemolytic disease (n = 16) were associated with markedly decreased plasma haptoglobin levels, without significant differences between intravascular vs. predominantly extravascular haemolysis. Diminished haptoglobin values were also observed in patients with liver cirrhosis, which normalized after liver transplantation. In contrast, markedly increased haptoglobin levels were found in patients with inflammation. In patients with haemolysis and a concomitant acute-phase response, however, haemolysis-dependent haptoglobin depletion was not attenuated. Interestingly, patients with a strongly positive direct antiglobulin test or high cold agglutinin titre but no further evidence for haemolysis had normal haptoglobin values. Likewise, anaemia owing to bone marrow failure, acute gastrointestinal or chronic diffuse blood loss, and end-stage kidney disease were associated with normal haptoglobin levels. Plasma haptoglobin depletion is a reliable marker for the instant diagnosis of accelerated red cell destruction irrespective of the site of haemolysis or the presence of inflammation. The capacity of this parameter to predict haemolysis appears to be limited in patients with liver cirrhosis and decreased haptoglobin production only.

Rituximab as Successful Therapy in a Patient with Refractory Paroxysmal Cold Hemaglobinuria.

Background: Paroxysmal cold hemaglobinuria (PCH) is caused by an IgG autoantibody which behaves as a biphasic hemolysin, attaching to RBCs at cold temperatures and activating complement at warmer temperatures, leading to hemolysis. This antibody, known as the Donath-Landsteiner antibody (DL-A), frequently shows specificity for the P-antigen. PCH was historically associated with syphilis infection. More recently, the DL-A has been found primarily in children with acquired autoimmune hemolytic anemia (AIHA) following a viral illness. In adults, PCH is rare and may occur as an idiopathic disease or in association with a lymphoproliferative disorder. Cases in children usually resolve spontaneously, whereas the adult form can be chronic and pose a therapeutic challenge, since treatment with steroids and splenectomy may be ineffective. Recently rituximab has been demonstrated to be a useful agent in treating AIHA that is resistant to conventional therapies. Case Report: A 64-year-old woman presented to another hospital with three months of progressive weakness. She was found to be severely anemic. Gastrointestinal blood loss was ruled out. Extensive work up was obtained with CT imaging and bone marrow biopsy, which showed no evidence of malignancy. A hemolytic process was identified and she was placed on oral prednisone 60mg daily. The patient then presented to Cedars-Sinai Medical Center three months later with recurrent fatigue and a hemoglobin concentration (Hb) of 6.6 g/dL. Lab values revealed an elevated reticulocyte count (7.9%), WBC 27.6, total bilirubin 3.5 mg/dL, indirect fraction 3.4 mg/dL, elevated LDH 445 U/L, absent haptoglobin, and microspherocytes on peripheral blood smear. The Direct Antiglobulin (Coombs) Test (DAT) was positive with an anti-complement reagent and negative with an anti-IgG reagent, leading to the suspicion of a DL-A or cold agglutinin. Cold agglutinin titer was normal. A Donath-Landsteiner test was positive, confirming the diagnosis of PCH. Steroids were rapidly tapered and she was given rituximab 375 mg/m2. Her Hb increased and evidence of hemolysis ceased. The patient received 3 additional doses of rituximab weekly. Her Hb recovered to normal. The patient did well for 9 months until she presented again with acute hemolysis (Hb 8.8 g/dL.) The DAT was again positive with an anti-complement reagent and negative with an anti-IgG reagent. She was given a single dose of rituximab with cessation of hemolysis. She received another 3 doses, which resulted in stabilization of her Hb. She remains well at 6 months follow-up.Discussion: The most frequent form of AIHA is due to a warm, IgG antibody and is commonly responsive to steroids or splenectomy, whereas in cold agglutinin disease, caused by an IgM antibody these therapies are usually ineffective. The use of rituximab has been reported as a useful treatment for both warm and cold AIHA refractory to conventional therapy. This is the first case report to our knowledge of a patient with adult PCH refractory to steroids successfully treated with rituximab. This patient responded dramatically to rituximab on two separate occasions, and has remained in remission since the second cycle after treatment with this single agent. Rituximab may represent an effective therapy for adult patients with chronic PCH.

Long-Term Follow up of Patients with Cold Agglutinin Disease.

Background: Data regarding long-term follow up of patients (pts) with cold agglutinin disease (CAD) are limited.Methods: We reviewed our institutional database of pts with CAD from 1981–2003. The diagnosis of CAD was confirmed by the following criteria: hemolysis and/or cold induced agglutination symptoms, cold agglutinin titre of ≥ 1:40, and typical direct anti-globulin test findings. We retrospectively collected pertinent clinical data including: demographics, dates of diagnosis and last follow up, associated hematologic diseases, baseline laboratory test results, treatment, clinical course, and subsequent development of lymphoproliferative diseases.Results: We identified 18 pts with CAD. Most (15) were females. The median age at diagnosis was 71.5 years (range, 22–92). While all pts presented with hemolysis, only 2 had cold-induced acral signs or symptoms. The median presenting hemoglobin level was 8.4 gm/dl (range, 4.5–13.5). The cause was considered idiopathic in 10 pts, while 8 pts had concomitant lymphoproliferative disorders at diagnosis: chronic lymphocytic leukemia, 1 pt; non-Hodgkin lymphoma (NHL), 3 pts; and monoclonal gammopathy of undetermined significance (MGUS), 5 pts. A serum protein electrophoresis was obtained in 16 pts. Five pts had monoclonal proteins, all IgM (3 κ, 2 λ). Thirteen (72%) pts required treatment for CAD or associated lymphoid malignancies at some point in the course of their disease. The most common treatments administered for CAD were prednisone (9 pts) and cyclophosphamide (3 pts). Prednisone produced an overall response rate of 78%. The responses were durable with a median of 95 months (range, 15–414). No one responded to cyclophosphamide. After a median follow up of 55.5 months (mean, 99.5; range, 12–449), 8 pts were alive, 5 in complete remission (2 maintained on prednisone), and 3 in partial remission (all off therapy). Of those who died (10 pts), only 1 died of CAD due to complications from severe anemia. Two pts subsequently developed lymphoproliferative diseases, MGUS (IgMk) and low grade NHL, 125 and 175 months after diagnosis, respectively. The clinical course of CAD did not seem to be any worse in pts with lymphoid malignancies.Conclusions: In our series, pts with CAD are frequently associated (44%) with lymphoproliferative disease at diagnosis. They have a relatively benign clinical course with a good likelihood of long-term disease remission. Unlike previous reports, prednisone is quite effective. Among those pts considered to have idiopathic CAD, a lymphoproliferative disease may develop later during the course of their disease.

Beneficial Effect of Rituximab in Combination with Oral Cyclophosphamide in Primary Chronic Cold Agglutinin Disease

Cold agglutinin disease (CAD) is an uncommon autoimmune hemolytic anemia characterized by B-cell proliferation. Conventional therapies for primary CAD such as corticosteroids, oral alkylating agents, splenectomy, interferon alpha, and plasma exchange are often ineffective at controlling the disease. The anti-CD20 monoclonal antibody rituximab (MabThera) depletes B-lymphocytes and thereby interferes with the production of cold agglutinin. We describe an elderly patient with primary (idiopathic) chronic CAD refractory to steroids who was successfully treated with 4 weekly infusions (375 mg/m2) of rituximab and 6 months of oral cyclophosphamide at a dosage of 60 mg/m2 per day. The increase in hemoglobin level and the decline in the plasma cold agglutinin titer were rapid (from the second rituximab infusion). The hematologic remission persisted for at least 8 months after treatment start, with no adverse effects. Rituximab and cyclophosphamide may be supplementary therapeutic modalities whose combination warrants further clinical investigation.

A Last Resort Modality Using Cryofiltration Apheresis for the Treatment of Cold Hemagglutinin Disease in a Veterans Administration Hospital

Cold hemagglutinin disease is a cold autoimmune hemolytic anemia (cAIHA) caused by an autoantibody, such as IgM, directed against the I-antigen present on the surface of erythrocytes. Cold exposure can activate this system causing hemolysis, hemagglutination, microvascular thrombosis, or acrocyanosis. Thus, surgical procedures requiring hypothermia, such as coronary artery bypass surgery, present a significant problem in patients with cAIHA. The purpose of this study was to evaluate the safety and effectiveness of cryofiltration apheresis (CFA), used as a last resort, for the treatment of cAIHA. Effectiveness was evaluated by clinical assessment and laboratory evaluations of cold agglutinin titer, immunoglobulins, and other plasma proteins. Safety was evaluated by vital signs, monitoring, and laboratory measurements of complements, hematology and blood chemistry. Five patients with cAIHA were treated by CFA using the cryoglobulin (CG) filter (Pall Medical, Ann Arbor, MI, USA). Four patients received only one CFA procedure, while one patient received four CFA treatments. The cold agglutinin titers were fairly low, ranging from 1 : 1 to 1 : 2048. However, a wide thermal amplitude(4-37 degrees C) was observed in most patients. Two out of five patients responded favorably with reduction in titer. The two responders had acute forms of cAIHA with serum positive for cryoglobulins. The three non-responders had chronic forms of cAIHA with negative cryoglobulins. CFA effectively removed cryoprotein precipitates while conserving other plasma components. The CG filter was biocompatible with no complement activation or observed complications due to CFA or CG filter. While the mechanism of action in treating this type of patient population with CFA is unknown, the plausible theories are discussed.

The immune haemolytic anaemias: a century of exciting progress in understanding.

The immune haemolytic anaemias: a century of exciting progress in understanding.

Inverse Association Between IgG–Anti-κ and Antierythrocyte Autoantibodies in Patients With Cold Agglutination

AbstractIt has been known for a long time that IgG–anti-F(ab′)2 antibodies (Abs) are able to suppress the B-cell response. We showed that natural IgG-anti–F(ab′)2 autoantibodies appear in the serum of patients with cold agglutination. If the anti-F(ab′)2 Ab suppresses cold agglutinin (CA)-producing B cells, one would expect an inverse correlation between the titers of these two Abs. Our study confirmed this correlation. Subsequent experiments showed that some anti-F(ab′)2 Abs bind to the hinge region of IgG. It was difficult to explain how this Ab suppresses CA-producing B cells, which are of IgM isotype. Here we show that patients with cold agglutination have an IgG–anti-κ light chain autoantibody in their serum. This is another member of the anti-F(ab′)2 Ab group. Because the vast majority of CAs are IgM-κ Abs, the anti-κ Ab might suppress CA-producing B cells. If this is the case, there should be an inverse association between the titer of anti-κ Ab and CA. In a group of 302 patients, we found that high titers of the anti-κ Ab correlate with low titers of CA and vice versa (P= .009). Interestingly, this association is found only in patients whose disease is caused by noninfectious agents, including mainly B-cell proliferations (P = .0058). Our data show that the inverse correlation is not confined to a particular CA autoantibody specificity. The results are discussed in the light of recent findings showing that anti-IgM Abs may either inactivate or kill tumoral B cells by apoptosis.

Inverse Association Between IgG–Anti-κ and Antierythrocyte Autoantibodies in Patients With Cold Agglutination

It has been known for a long time that IgG–anti-F(ab′)2 antibodies (Abs) are able to suppress the B-cell response. We showed that natural IgG-anti–F(ab′)2 autoantibodies appear in the serum of patients with cold agglutination. If the anti-F(ab′)2 Ab suppresses cold agglutinin (CA)-producing B cells, one would expect an inverse correlation between the titers of these two Abs. Our study confirmed this correlation. Subsequent experiments showed that some anti-F(ab′)2 Abs bind to the hinge region of IgG. It was difficult to explain how this Ab suppresses CA-producing B cells, which are of IgM isotype. Here we show that patients with cold agglutination have an IgG–anti-κ light chain autoantibody in their serum. This is another member of the anti-F(ab′)2 Ab group. Because the vast majority of CAs are IgM-κ Abs, the anti-κ Ab might suppress CA-producing B cells. If this is the case, there should be an inverse association between the titer of anti-κ Ab and CA. In a group of 302 patients, we found that high titers of the anti-κ Ab correlate with low titers of CA and vice versa (P= .009). Interestingly, this association is found only in patients whose disease is caused by noninfectious agents, including mainly B-cell proliferations (P = .0058). Our data show that the inverse correlation is not confined to a particular CA autoantibody specificity. The results are discussed in the light of recent findings showing that anti-IgM Abs may either inactivate or kill tumoral B cells by apoptosis.

抗ＨＩ抗体による寒冷凝集素症にＩＴＰを合併したＥｖａｎｓ症候群の１例

A 70-year-old female was admitted with anemia and thrombocytopenia. Her blood type was B Rho (+). Her RBC was 250×104/μl, Hb7.8g/dl, Ht 23.2%, Retic. 55‰, WBC 2900/μl, T. bil 0.3mg/dl, LDH 917U/L, and Haptoglobin <10mg/dl. Cold agglutinin titer was×1024, direct Coombs test (-), indirect Coombs test (4+). Antibody screening test in saline revealed serum agglutinated adult O cells (4+) (×512), adult i cells (+) (×64), cord cells (-) and B cells (-), leading to an antibody diagnosis of anti-HI antibody. She subsequently developed thrombocytopenia (16×103/μl) and PAIgG was 54.8ng/107 platelets, giving a diagnosis of idiopathic thrombocytopenic purpura together with cold agglutin disease. The presence of cold agglutinin disease due to anti-HI antibody and development of ITP indicated this to be a case of Evans syndrome. Hemolytic anemia due to anti HI antibody is very rare, as is the association of ITP with cold agglutination disease.

Mycoplasma pneumoniae respiratory infection.

1. Nevio Cimolai, MD* 1. 2. *Director, Program of Microbiology, Virology, and Infection Control, Children’s and Women’s Health Centre of British Columbia, Vancouver, BC, Canada. 1. Mycoplasma pneumoniae remains the most common treatable cause of community-acquired atypical pneumonia in children. 2. Common features of M pneumoniae pneumonia include bilateral pulmonary involvement, multifocal or diffuse disease, and reticular infiltrates, but the radiologic manifestations are considerably more diverse. 3. Extrarespiratory manifestations potentially can include several body systems (eg, varied exanthemata, meningoencephalitis, arthropathy). These are either shortly preceded by or coexist with an active respiratory infection. 4. Cold agglutinin serology is of limited diagnostic value for children. 5. Erythromycin and tetracycline remain effective antimycoplasmal antibiotics; beta-lactam agents are not of value. One would anticipate that almost 4 decades of research and clinical experience should leave very little room for ongoing investigation of Mycoplasma pneumoniae . Nevertheless, respiratory infection caused by this pathogen remains common, and advances in science continue as unique attributes of the bacterium and the associated clinical illness unfold. Microbiologic and subsequently other investigations possibly have been delayed in part by the nature of the bacterium. Mycoplasmas are the smallest bacteria, and M pneumoniae in particular is sufficiently fastidious in vitro that few laboratories have provided culture services. Whereas Escherichia coli from a urine sample or Streptococcus pneumoniae from a cerebrospinal fluid specimen may be cultivated luxuriously in 18 to 24 hours, the isolation of M pneumoniae from sputum may require 7 to 21 days. These small, cell wall-deficient bacteria are impossible to visualize in respiratory secretions by either Gram stain or other light microscopic methods. In contrast to the rigid structure of other bacteria, mycoplasmas are pleomorphic (Fig. 1⇓ ). Indeed, the name mycoplasma refers to the plasticity of bacterial forms that crudely resemble some fungal filaments. Mycoplasmas, however, are not even remotely related to or even minimally resemble mycobacteria (eg, Mycobacterium tuberculosis ) or mycologic (ie, fungal) pathogens with respect to most other attributes. The lack of cell wall …

Cold agglutinins in rhesus macaques infected with simian immunodeficiency virus (SIV)

Cold agglutinins are uncommon autoimmune phenomena associated with mycoplasma pneumonia, viral infections, lymphoproliferative neoplasia and recently, acquired immunodeficiency syndrome (AIDS) in human beings. Six rhesus macaques infected with pathogenic isolates of simian immunodeficiency virus (SIV) developed cold agglutinins late in the course of viral infection in association with hyperproteinaemia, hyperglobulinaemia and thrombocytopenia. Cold agglutinin titres ranged from 1:1024 to 1:8192. The development of cold agglutinins in SIV-infected rhesus macaques may be another manifestation of immune dysfunction in this non-human primate model of AIDS.

Clinical features of Japanese patients with chronic cough induced by gastroesophageal reflux

ABSTRACT Gastroesophageal reflux (GER) has been reported as a cause of chronic cough (CC) in the United States. It has been reported that 5–21% of CC cases are induced by GER. In Japan, however, detailed clinical features of CC induced by GER have not been described. The present study reports on six Japanese patients with GER-induced CC. The subjects were all females, with a mean age of 72 years. The average body mass index was 37 kg/m 2 , indicating obesity. No abnormalities were found with regard to concentrations of C-reactive protein, peripheral eosinophil counts, serum IgE concentrations, serum titers of cold agglutinins or antibodies to Mycoplasma pneumoniae, chest radiograph findings, respiratory function tests or blood gas analyses. Bronchial biopsy was performed in three patients and showed chronic inflammation characterized by lymphocytic infiltration, squamous metaplasia and mucosal basement membrane thickening. In the study population (Japanese patients), GER-induced CC tended to occur in elderly obese women and may be attributable to airway inflammation.

Inverse correlation between IgG-antihinge region and antierythrocyte autoantibody in chronic benign and malignant cold agglutination.

Previous reports provided evidence of an immunosuppressive role of natural anti-F(ab')2 antibodies. If suppressive anti-F(ab')2 antibodies also regulated the autoantibody production in cold agglutination, one would expect high titers of anti-F(ab')2 to be associated with low titers of cold agglutinins. Indeed, our previous studies revealed an inverse correlation between IgG-anti-F(ab')2 and cold agglutinins. Many previous experiments focused on anti-F(ab')2 of an antiidiotypic nature. Recent epitope mapping showed that anti-F(ab')2 of healthy persons is not an antiidiotype but recognizes a hinge region sequence. We attempted to answer the question whether this IgG-antihinge antibody is responsible for the previously described association between anti-F(ab')2 and cold agglutinins. IgG-antihinge and IgG-anti-F(ab')2 antibody was determined and statistically analyzed in the serum of 334 patients with cold agglutination. Our experiments revealed a strong correlation between the concentrations of antihinge and the previously described anti-F(ab')2 antibody. The anti-F(ab')2 activity was competitively inhibited by a synthetic hinge peptide. Moreover, patients with high antihinge titers had low cold agglutinin titers, and vice versa. A stratification according to cold agglutinin specificity and disease etiology showed that the inverse correlation is present only in anti-I and anti-i patients suffering from monoclonal B-lymphocyte proliferation. In conclusion, our results confirm the correlation previously described for anti-F(ab')2 antibody and antierythrocyte autoantibody and define for the first time an association between an idiotype-independent anti-IgG autoantibody and cold agglutinin.

Do cold agglutinins have any impact on the outcome of liver transplantation?

Cold agglutinins, IgM red blood cell autoantibodies, cause cold agglutinin disease with hemolysis and microvascular occlusion. Cold preservation of kidneys during renal transplantation in the presence of cold agglutinins can cause graft malfunction. However, the impact of cold agglutinins on the outcome of liver transplantation is unknown. We measured the pretransplant presence and titer of cold agglutinins in 327 primary liver allograft recipients and analyzed their relationship to outcome after transplant. Thirty-three percent of pretransplant patients had cold agglutinins. Cold agglutinins were more common in patients with viral-related liver diseases (49%) compared with those with nonviral-related liver disease (32%). There was no difference between recipients with and without cold agglutinins in usage of blood products, postoperative day 2 aminotransferase levels, acute rejection at day 7, the development of hepatic artery thrombosis, nonanastomotic biliary strictures, or 4-month allograft survival. In conclusion, cold agglutinins are common in liver transplant patients before surgery, especially those with viral-related liver diseases. However, the presence of cold agglutinins does not impact on outcome after liver transplantation.

The Clinical Characteristics of Mycoplasmal Pneumonia in Adults

BACKGROUND: The incidence of mycoplasmal pneumonia is predominantly at childhood and early adulthood, but in adults, its incidence is low and its symptoms and physical findings are nonspecific. The definite diagnosis of M. pneumoniae pneumonia can be made by sputum culture, but requires several weeks for positive results, and the early diagnosis must initially be based on the serologic tests and appropriate clinical findings. Thus, we evaluated the clinical aspects of M. pneumoniae pneumonia in the adults patients. METHOD: Among the admitted patients due to pneumonia, the definite diagnosis is anti-M. pneumoniae antibody titer of > 1:40 and a single cold agglutinin titer of > 1:64. The presumptive diagnosis is anti-M. pneumoniae antibody titer of > 1:40 or a single cold agglutinin titer of > 1:64 and the clinical characteristics or chest X-ray findings are compatible with M. pneumoniae pneumonia. We studied the age and sex distribution, seasonal distribution, clinical symptoms, physical findings, serologic test, chest X-ray findings, treatment and its progression. RESULTS: 1) The age distribution was even and the ratio of male to female was 1:1. 2) The monthly distribution was most common in January(16.7%) and the seasonal distribution in autumn and winter(autumn: 30%, winter: 33.3%). 3) The cold agglutinin titers were higher than 1:64 in 12 cases(40%), and reached the peak level around 2 weeks from onset and antimycoplasma antibody titers were higher than 1:160 in 5 cases(16.7%). 4) On the chest X-ray, pulmonary infiltration was noted in 28 cases(93.3%) among 30 cases and right lower lobe involvement was the most common(33.3%) and both lower lobe involvement was noted in 7 cases(23.3%). 5) The mean treatment duration was most common(33.3%) in 1 week to 2 weeks after admission and 26 cases(86.7%) were improved within 4 weeks. 6) On admission, there was fever(> or =38.9degreesC) in 17 cases(56.7%), and the fever subsided in 12 cases(70%) within 3 days after treatment using erythromycin. CONCLUSION: The mycoplasmal pneumonia in adults shows milder clinical patterns than that in childhood and can be completely recovered without complication by early diagnosis and treatment.

Red cell destruction in cold agglutinin disease.

The severity of autoimmune hemolytic anemia (AIHA) caused by cold agglutinins (CAs) is known to differ markedly in chronic CA disease as well as in postinfection cold agglutination. The various cold agglutinin specificities and mechanisms of red cell destruction are described. Original papers and reviews of the German and English literature (Medline research); own results. Original papers and reviews of the recent years on studies of the biochemistry and specificity of CAs and the pathophysiology of AIHA. A crucial point for the severity of AIHA caused by CAs is the CA-binding capacity to red cells in vivo. This is reflected by the serologic behavior of the actual CA in vitro, represented by its thermal amplitude. Because most CAs are IgM molecules, red cell destruction by CAs is limited to mechanisms initiated by complement (C) activation. In recent years, several CA specificities, in addition to anti-I/i, have been identified on a serological and biochemical basis. CAs of the IgG and rarely of the IgA isotypes have been found. The CA-induced red cell destruction does not only depend on CA titer or its thermal amplitude. The severity of CA-induced AIHA may also depend on CA isotype and/or specificity. Therefore, the complement activation capacity of CAs with a given isotype but different specificities has to be elucidated in further studies.