Presence of anti-FKBP12 autoantibodies in patients with liver allografts: its association with allograft rejection

BACKGROUND: It was reported that autoantibodies against cyclophilin are present in sera from systemic lupus erythematosus. We hypothesized that autoantibodies against FKBP12, another immunophilin, may be present in the plasma of liver allograft recipients, which may affect the clinical outcome of liver allografts. METHODS: We investigated the relationship between the presence of anti-FKBP12 autoantibodies and rejection episodes in 47 patients treated with FK506 after living-related partial liver transplantation (LRLT). The patients consisted of two groups: 22 with rejection [R(+) group] and 25 without rejection [R(-) group]. The autoantibodies were measured by an indirect ELISA, and the specificity was confirmed by absorption with antigen and immunoblotting. RESULTS: The autoantibodies were detected in 13 of 22 in the R(+) group (IgG: 5; IgM: 6; both: 2) and in 6 of 25 in the R(-) group (IgG: 2; IgM: 3; both: 1) before LRLT (P=0.0193). After LRLT, they were also detected more frequently in the R(+) group (12 of 22; IgG: 1; IgM: 8; both: 3) than in the R(-) group (2 of 25; IgG: 1; IgM: 1) (P=0.001). In the R(+) group, the mortality of the patients who were positive and negative for the autoantibodies was 6 of 12 and 2 of 10, respectively. The autoantibodies were detected in all four patients with chronic or refractory acute rejection. The autoantibodies were not detected in any of the 34 healthy subjects. CONCLUSIONS: These results suggest that the presence of the autoantibodies in patients before transplantation is related to rejection, and the presence after transplantation may be associated with patient outcome.     

Partial hepatic resection for ischemic graft damage after liver transplantation: a graft-saving option?

BACKGROUND: Intrahepatic biliary strictures or parenchymal infarcts may occur after liver transplantation as a complication of ischemic damage to the graft. In some selected cases the lesions appear to be confined to a part of the liver. We report our experience with partial graft resection in this setting. METHODS: From January 1984 to December 1991, 286 liver transplantations were performed in 257 recipients. Seven patients, three children and four adults, underwent partial hepatectomy 3 to 218 weeks after liver transplantation of a full-size graft. The clinical presentation included septic parenchymal infarcts (n = 4) and nonanastomotic biliary strictures (n = 3) complicating (n = 5) artery thrombosis or not (n = 2). There were four left hepatectomies, two left lobectomies, and one right hepatectomy. In four instances partial hepatectomy was performed after failed attempt at biliary reconstruction (n = 2) or arterial revascularization (n = 2). Partial graft resection was performed extrafascially without Pringle's maneuver and mobilization of the remnant liver to preserve its vascularization. RESULTS: No surgical complications occurred, and none of the patients experienced acute hepatic failure during the postoperative period. All patients were discharged home 10 to 96 days (median, 23 days) after liver resection. Two patients had recurrent ischemic cholangitis. One patient underwent successful regrafting for recurrent Budd-Chiari syndrome; one patient died of tumor recurrence. Six patients were alive with a follow-up ranging from 12 to 45 months. CONCLUSIONS: These results suggest that partial graft resection is a safe and graft-saving option after liver transplantation in selected patients with localized ischemic damage of the graft.     

False increase in C-reactive protein attributable to heterophilic antibodies in two renal transplant patients treated with rabbit antilymphocyte globulin

Increased serum C-reactive protein (sCRP) is a sensitive marker of renal graft rejection. We describe the cases of two children with uncomplicated renal transplantation who had false-positive sCRP values on analyzers using rabbit anti-CRP but values within the reference range with anti-CRP from other animal species. Cross-reaction with heterophilic antibodies was suggested by clinical and biological signs of serum sickness and daily treatment with rabbit antilymphocyte globulin (ALG). The interference depended on the serum concentration of the cross-reactant and was removed by subtotal IgG adsorption to Protein A or Protein G or by immunoadsorption using rabbit ALG or total IgG in non-immune rabbit serum. Anti-rabbit IgG and IgM antibodies were detected in both patients. These are the first reported cases of cross-reaction with heterophilic antibodies in a turbidimetric CRP assay.     

Vascular complications of kidney transplantation

584 kidney transplantations (208 from cadaveric donors, 376 from living relative donors) were performed in Medical Faculties of the Istambul University in 1986-1997. Thrombosis of the renal artery was observed in 2 patients (0.35%). One of them had diffused arterial atherosclerosis 4 months after the kidney transplantation. In spite of two successful thrombectomies, the patient died 3 months after the last surgical procedure from cerebral thrombosis. The other patient underwent nephrectomy. Hypertension was observed in 63 patients. In 5 of them about 50% stenosis of the anastomotic area was detected by doppler duplex scan and selective angiogram. Transluminal angioplasty was performed in one patient, open surgical correction in one case. Renal vein thrombosis took place in 1 (0.2%) patient. In 2 cases (0.35%) 5 and 12 years after the transplantation aortic aneurysmal dissection was observed.     

Study of the beta -delayed neutron decay of 18N

The shortage of suitable liver donors for children has motivated the use of ABO-incompatible (ABO-I) grafts for transplantation in urgent situations. However, survival after ABO-I liver grafts has been reported at about 30% as compared with 80% in cases of ABO-identical or -compatible liver grafts. This difference has been attributed to antibody-mediated, hyperacute or chronic liver rejection, due to preformed ABO antibodies (alloantibodies). In this study, we report our results with ABO-I livers in children without alloantibodies at the time of transplantation. From January 1988 to June 1993, 143 OLT were performed in 122 children. Eight children received 8 ABO-I liver grafts. Of these, 7 patients were included in the study. All 7 were alloantibody free before OLT. Five children were spontaneously alloantibody free, while in 2 children, the plasma alloantibodies were eliminated before and after transplantation using intravenous infusion of specific blood group antigens of the donor blood group (soluble antigens). Immunosuppression consisted of a triple-drug treatment combining CsA, AZA, and steroids. The follow-up period was between 10 and 48 months. One child died from a surgical complication. Six children survived, but 1 died 10 months later from intestinal obstruction. There were no graft losses and no episodes of hyperacute or chronic rejection. The graft and patient survival rate was 71%. There was a 28% incidence of rejection, but all were mild (requiring steroid boluses only). Our results suggest that the absence of ABO alloantibodies at the time of and after transplantation can protect ABO-I liver grafts against antibody-mediated rejection, whether hyperacute or chronic, and that soluble antigens are effective in eliminating alloantibodies in children.     

Detection of immunoglobulin M antibodies to glycoprotein G-2 by western blot (immunoblot) for diagnosis of initial herpes simplex virus type 2 genital infections

Western blots (immunoblots) for the detection of immunoglobulin M (IgM) antibodies specific for herpes simplex virus type 1 (HSV-1) and HSV-2 in patients' sera were developed. The locations of the type-specific glycoprotein G (gpG-2) of HSV-2 (92- and 140-kDa forms) and glycoprotein C of HSV-1 (gpC-1), which carries mostly type-specific antigenic epitopes, were checked with specific monoclonal antibodies. Western blot assays for IgM antibody to gpC-1 or gpG-2 were performed after depletion of IgG by precipitation with anti-human IgG. In patients with primary HSV-2 genital infections, seroconversion of IgM and IgG antibodies to both the 92- and 140-kDa forms of gpG-2 was observed, although both antibodies appeared in convalescent-phase serum after the first week. IgM and IgG antibodies to low-molecular-size polypeptides (40 to 65 kDa) were the first antibodies observed in patients with primary infection, but these antibodies were cross-reactive with HSV-1 and HSV-2. However, in patients with recurrent HSV-2 infections, IgG antibodies to both forms of gpG-2 and the low-molecular-size polypeptides were found no matter how early after onset the patient was bled, and IgM to gpG-2 did not appear. In patients with nonprimary initial genital HSV-2 infections, IgG antibody to HSV-1 was demonstrated in the first serum specimen, and HSV-2-specific IgM was found in 39% of the serum specimens. Hence, the Western blot assay can be used to test for IgM antibody to gpG-2, allowing for the retrospective diagnosis of inital HSV-2 infections and its use as a supplementary test to the gpG-2 IgG enzyme-linked immunosorbent assays developed elsewhere. In contrast, IgM antibody to gpG-2 is not usually detected in patients with recurrent HSV-2 infections.     

America: where kids are getting killed

Two cases of liver metastasis from colon cancer were treated by percutaneous ethanol (PEI) and acetic acid (PAI) injection for the recurrent lesion after surgery. Case 1 was a 60-year-old female who received sigmoidectomy with partial hepatectomy, and intraarterial 5-FU infusion was done after surgery. One year later, recurrence of liver tumor was detected, and PEI and PAI were performed for the metastatic lesions of the liver. Tumor regression and histopathological examination revealed coagulative necrosis. The patient died of lung metastasis 2 years and 10 months after treatment. Case 2 was a 58-year-old-male with ascending colon cancer and liver metastasis, who received surgery, and chemotherapy with intraarterial 5-FU infusion was continued. Four months later, recurrence of liver metastasis with elevation of serum CEA was noted. The patient received PEI three times and CEA decreased. Re-operation of hepatectomy revealed complete necrosis at the site of PEI. The patient has been alive for 1 year and 6 months with a new recurrence in the liver and is receiving repeated PEI therapy. PEI and PAI seem to be useful for the treatment of unresectable liver metastasis.     

Hepatic artery thrombosis in living related liver transplantation

BACKGROUND: Hepatic artery thrombosis (HAT) after orthotopic liver transplantation remains a significant cause of graft loss in pediatric patients. We previously reported that the microsurgical techniques for arterial anastomosis can reduce the incidence of HAT in living related liver transplantation (LRLT). The purpose of this study is to analyze the risk factors for HAT after LRLT. A total of 245 patients received 250 liver transplants. METHODS: Eight arteries in eight patients, reconstructed with the use of loupe magnification (HAT; 1/8, 12.5%), were excluded from this study. We observed HAT in 4 patients of the 242 transplants (1.7%, HAT group). Seventeen factors were compared between the HAT and the control group (those without HAT). RESULTS: HAT occurred in 3 of 33 grafts (9%) from ABO-incompatible donors, whereas it occurred in 1 of 209 grafts (0.5%) from identical or compatible donors (P=0.008). The corrected volume of fresh-frozen plasma intraoperatively transfused in the HAT group (46.9+/-30.3 ml/kg) was significantly (P=0.015) different from that in the control group (10.2+/-1.9 ml/mg). In all four patients with HAT, emergent revisions of the anastomosis were performed. Two patients with ABO-incompatible grafts died of hepatic failure and sepsis. CONCLUSIONS: Although microsurgical techniques can minimize the surgical risk factors for HAT, overtransfusion of fresh-frozen plasma in high-risk patients (ABO incompatible) may be a critical factor in the development of HAT in LRLT.     

Improving results of pediatric renal transplantation

BACKGROUND: Outcome after renal transplantation in children has been variable. We undertook a retrospective study of our experience over the past five years. STUDY DESIGN: From January 1, 1988, to October 15, 1992, 60 renal transplantations were performed upon 59 children at the Children's Hospital of Pittsburgh. Twenty-eight (47 percent) of the kidneys were from cadaveric donors, and 32 (53 percent) were from living donors. The recipients ranged in age from 0.8 to 17.4 years, with a mean of 9.8 +/- 4.8 years. Forty-six (77 percent) recipients were undergoing a first transplant, while 14 (23 percent) received a second or third transplant. Eight (13 percent) of the patients were sensitized, with a panel reactive antibody of more than 40 percent. Eleven of the 14 patients undergoing retransplantation and seven of the eight patients who were sensitized received kidneys from cadaveric donors. Thirty-three (55 percent) patients received cyclosporine-based immunosuppression, and 27 (45 percent) received FK506 as the primary immunosuppressive agent. RESULTS: The median follow-up period was 36 months, with a range of six to 63 months. The one- and four-year actuarial patient survival rate was 100 and 98 percent. The one- and four-year actuarial graft survival rate was 98 and 83 percent. For living donor recipients, the one- and four-year actuarial patient survival rate was 100 and 100 percent; for cadaveric recipients, it was 100 and 96 percent. Corresponding one- and four-year actuarial graft survival rates were 100 and 95 percent for the living donor recipients and 96 and 69 percent for the cadaveric recipients. Patients on cyclosporine had a one- and four-year patient survival rate of 100 and 97 percent, and patients on FK506 had a one- and three-year patient survival rate of 100 and 100 percent. Corresponding one- and four-year actuarial graft survival rates were 100 and 85 percent in the cyclosporine group, while one- and three-year actuarial graft survival rates were 96 and 84 percent in the FK506 group. The mean serum creatinine level was 1.24 +/- 0.64 mg per dL; the blood urea nitrogen level was 26 +/- 13 mg per dL. The incidence of rejection was 47 percent; 75 percent of the rejections were steroid-responsive. The incidence of cytomegalovirus was 10 percent. The incidence of post-transplant lymphoproliferative disorder was 8 percent. None of the patients on cyclosporine were able to be taken off prednisone; 56 percent of the patients receiving FK506 were taken off prednisone successfully. Early growth and development data suggest that the patients receiving FK506 off prednisone had significant gains in growth. CONCLUSIONS: These results support the idea that renal transplantation is a successful therapy for end-stage renal disease in children. They also illustrate the potential benefits of a new immunosuppressive agent, FK506.     

Repairing bone defect with autogenous periosteal pieces in coagulum: experimental study and clinical application

Sixty patients who received 75 consecutive liver grafts and had routine Doppler sonography monitoring in the early postoperative period (three times a day) were reviewed for vascular complications. Thrombosis of the hepatic artery was detected in seven patients (3, 4, 20, 24, 48, 70 and 84 h after liver transplantation) and was then confirmed by emergency laparotomy in six cases. In one patient, thrombosis was verified by angiography before laparotomy. In two patients thrombectomy was successful, in five patients retransplantation had to be performed. Portal vein occlusion was detected in three patients (24, 26 and 90 h after transplantation) and all were successfully treated by thrombectomy and partial arterialization of the portal vein. Colour Doppler sonography was associated with no false-positive or -negative results. The specificity was 100% for the diagnosis of hepatic artery and portal vein thrombosis. In our opinion colour Doppler sonography will be able to replace time-consuming angiography in vascular diagnostics in the early postoperative phase after liver transplantation. Furthermore, there is evidence that frequent use of this non-invasive technique permits early detection of clinically unsuspected vascular complications and subsequent immediate relaparotomy, which is linked to a reduction in the rate of retransplantation.     

Reversible brainstem auditory evoked potential abnormalities in jaundiced Gunn rats given sulfonamide

Renal transplantation therapy performed for amyloid nephropathy is controversial because of the fatal effects of the disease. Amyloidosis is a relatively frequent disease and is generally associated with familial Mediterranean fever (FMF) in Turkey. Renal transplantation in the treatment of amyloid nephropathy started in January 1985. Till now, 18 (3.2%) renal transplantations have been performed on patients who had amyloid nephropathy. The mean follow-up period was 34.6 months. Fourteen renal grafts still function well (creatinine: 1-3.2 mg/dL). The overall 1-year patient and graft survival rates were 88.9% and 83.0%, respectively. These rates are not statistically different from renal transplantations done for other cases of renal failure. Therefore, patients with end-stage renal failure due to amyloidosis can be considered as appropriate candidates for renal transplantation.     

Methyl tert-butyl ether (MTBE) contamination in private wells near gasoline stations in upstate New York

BACKGROUND: Auxiliary liver transplantation has several advantages over standard orthotopic liver transplantation. However, functional competition has been reported even in auxiliary partial orthotopic liver transplantation (APOLT). We evaluated herein the interaction in APOLT between the native liver and the graft in terms of portal blood flow and regeneration. The need for diversion of the portal blood flow to the graft was also assessed. METHODS: A total of 15 patients received APOLT from living donors. Portal blood flow to the native liver was preserved in 6 patients, and the portal vein to the native liver was preemptively transected at the time of transplantation in 9 patients. RESULTS: Of the patients with preservation of the portal blood flow to the native liver, two showed inadequate graft portal blood flow just after operation, and in the other three patients the graft portal blood flow decreased or the graft atrophied after deterioration of the graft function. In the patients with preemptive transection of the portal vein to the native liver, optimal graft portal blood flow was obtained, and the native liver, supplied only by arterial inflow, supported a small-for-size graft until the graft regenerated. The damage to the native liver was minimal. CONCLUSIONS: Functional competition may occur in APOLT with preservation of the portal blood flow to the native liver, whereas preemptive transection of the native liver portal vein is a safe procedure and effectively prevents the portal steal phenomenon.     

Complete neurological recovery of an adult patient with type II citrullinemia after living related partial liver transplantation

Type II citrullinemia is an adult-onset hepatocerebral disease caused by a deficiency of argininosuccinate synthetase in liver. A 25-year-old Japanese man suddenly developed encephalopathy, showing disorientation and flapping tremor. Plasma concentrations of ammonia and citrulline were extremely high, and hepatic argininosuccinate synthetase activity was deficient. The patient's condition deteriorated rapidly in spite of intensive medications. Therefore, we performed a partial liver transplantation using a graft obtained from his healthy 61-year-old father. After surgery, his neurological symptoms soon disappeared and plasma levels of ammonia and citrulline were normalized within 3 months after operation. Type II citrullinemia is one fulminant form of various liver-based metabolic diseases, and immediate liver transplantation is necessary to rescue patients with this disease. As liver transplantation from cadaveric donor is still not possible in Japan, it seems justifiable to use living related partial liver transplantation for our patient.     

C-13 Methanol Far-Infrared Laser: Newly Discovered Lines, Predictions, and Assignments

Autologous blood donation before elective surgery is generally believed to be a safe procedure for patients with a variety of underlying medical conditions, but the accumulation of additional data continues to define its safety in unique patient groups. Patients who have received a solid organ transplant may also undergo various elective surgical procedures after transplantation, and the question of safety of autologous blood donation for these patients is raised. In one hospital-based blood collection program, we identified 4 patients who had received solid organ transplants and subsequently made autologous blood donations for elective operations unrelated to the transplantation. Two patients had received heart transplants and 2 received liver transplants. A total of 10 autologous donations were made by these 4 patients without adverse effects or complications. A low hemoglobin concentration was the only reason for temporary deferral from autologous donation. Despite having complicated clinical situations, recipients of solid organ transplants can safely donate autologous blood and should not be automatically excluded from making such donations.     

Immunoglobulin M antibody response to hepatitis C virus core protein in patients with chronic hepatitis C

We retrospectively assessed the frequency and clinicopathologic and virologic significance of production of immunoglobulin M (IgM) antibody to hepatitis C virus (HCV) core protein in patients with chronic hepatitis C. Sera from 60 patients with chronic hepatitis C were tested for IgM anti-HCVcore (anti-HCc). Twenty of these patients received ribavirin plus interferon-alpha for 24 weeks, and were classified as sustained, transient, or nonresponders on the basis of alanine aminotransferase levels and the presence of HCV RNA at the end of treatment and 24 weeks later. IgM anti-HCc was detected in 21 patients. There was no correlation between the presence of IgM anti-HCc and clinical features such as sex, age, mode of transmission, serum levels of alanine aminotransferase, HCV genotype, serum HCV titer, or histologic findings. Among the patients who received ribavirin plus interferon-alpha, the mean IgM anti-HCc level before therapy was comparable between sustained (n = 10), transient (n = 8), and nonresponders (n = 2). A statistically significant decrease in IgM anti-HCc response during antiviral therapy was observed in the 18 responders who became negative for serum HCV RNA at the end of therapy. These data suggest that IgM anti-HCc is of limited clinical usefulness as a marker of chronic HCV infection. Serial testing for IgM anti-HCc may provide a marker of antiviral response.     

Hepatitis C--associated glomerular disease in liver transplant recipients

Hepatitis C virus (HCV) infection may be associated with extrahepatic illness including renal disease. We investigated the clinical and virological characteristics of three patients who developed a mesangial proliferative and sclerosing glomerulopathy alone or in association with membranoproliferative glomerulonephritis after liver transplantation for end-stage liver disease secondary to HCV infection. Using polymerase chain reaction technology and the IgM RIBA assay, viral load, genotype and IgM antibody response to HCV in the setting of glomerulonephritis was evaluated. Within 1 year of transplantation, the patients showed decreased renal function, proteinuria and recurrent hepatitis C liver disease. Likewise, HCV viral load increased following transplantation, whereas the viral genotypes remained unchanged. Although the first patient presented with classic type II cryoglobulinemia in association with glomerulonephritis, the second patient developed an IgM directed specifically against the hepatitis C core antigen. The third patient developed a low-titered IgM directed against the hepatitis C core antigen with rheumatoid factor activity but without cryoglobulinemia. All of the patients show IgM in glomerular capillary walls by biopsy. One patient has shown a clinical response to interferon (IFN) alfa-2b therapy without evidence of hepatic allograft rejection. The second and third patients have not responded to IFN or developed hepatic rejection. This study suggests that HCV-associated glomerulonephritis may complicate liver transplantation in conjunction with the production of increased amounts of IgM of variable specificity. The posttransplant setting may provide a unique situation in which to investigate the specific requirements for the onset of renal disease.     

Quantitative criteria of a rhinocytogram of healthy subjects

Cytomegalovirus infection (CMV) complicated the posttransplant course in 9 of 24 children after liver transplantation. We found specific antibodies (IgG and IgM) to be of very low value in diagnosis and monitoring of CMV infection after liver transplantation. Detection of CMV-DNA by PCR method in the blood or urine was very useful for diagnosis, but less for monitoring of the course of disease and its treatment. Measurements of early immediate CMV antigen (IEA), in peripheral blood leucocytes allowed for very early diagnosis of CMV infection and correlated well with the course of disease and response to treatment of the patient.     

Preoperative portal embolization: an effective means for inducing hypertrophy of the healthy liver and increasing indications for hepatic resection]

BACKGROUND: This study was carried out to investigate the efficacy and safety of high-dose chemotherapy (HDC) for the treatment of patients with advanced testicular cancer. METHODS: Seven patients were treated with high-dose carboplatin, etoposide, and ifosfamide followed by autologous blood stem cell transplantation. One patient received 1 cycle, 4 patients received 2 cycles, and 2 patients received 3 cycles of HDC. We performed a total of 15 autologous blood stem cell transplantations: 8 with autologous bone marrow; 6 with peripheral blood stem cells; and 1 with peripheral blood stem cells in addition to autologous bone marrow. RESULTS: Four of the 7 patients achieved a pathologic complete response via early use of HDC and additional salvage surgery. All 4 patients are still alive without evidence of disease at 12, 30, 33, and 54 months, respectively. One patient is alive with active disease at 35 months. Two patients refractory to conventional chemotherapy died of progressive disease at 5 and 27 months, respectively. The hematologic recovery after HDC was rapid, and peripheral blood stem cells tended to have shorter hematologic recovery compared with those from autologous bone marrow, although the difference was not significant. Nonhematologic toxicity was usually mild and manageable. CONCLUSION: High-dose chemotherapy, followed by autologous blood stem cell transplantation, may be safe and effective for patients with advanced testicular cancer, particularly when early use of HDC is conducted for chemotherapy-sensitive patients. A further large, long-term, follow-up study will be needed to define the role of HDC.     

Studies of immunoglobulins, bentonite flocculation and IgE, IgG and IgM antibodies in serum from patients with trichinosis

Serial serum samples were obtained from two patients from a family of four who ingested raw pork at a known time and in whom trichinosis developed. Single and occasionally two serum samples were obtained from other patients with proved trichinosis. Studies of these serum samples showed that elevations of serum immunoglobulin E (IgE) levels do occur but not in all serum samples and that even when these levels are elevated, they are not high enough to be of diagnostic value. This is also true for serum immunoglobulin M (IgM). Using a solid phase radioimmunoadsorbent test, IgE, IgG and IgM antibodies were detected in the serums. The IgE antibody activity appeared early but was not present in all samples. The IgM antibody activity appeared later than the IgE and IgG antibody activity, and there was a statistically significant correlation between IgM antibodies as determined by radioimmunoassay and the bentonite flocculation titers suggesting that the bentonite flocculation is due to IgM antibody. IgM antibodies detected by radioimmunoassay were positive in all serum samples from patients with trichinosis except for a sample obtained 3 days after the onset of symptoms. The early increase in IgG antibodies and the occurrence of these antibodies in all serum samples obtained more than 3 days after onset of symptoms suggest a potential diagnostic use if serial samples are available early in the course of the disease.     

Detection of isotype-specific autoantibodies to calpastatin in sera from patients with rheumatic diseases using heat-treated HeLa cell extract as an antigen source for immunoblotting

To detect immunoglobulin isotype-specific autoantibodies to native human calpastatin in patients with rheumatic diseases, we performed immunoblot analysis using the heated HeLa cell extracts to enrich heat-resistant calpastatin. The calpastatin molecule that was apparently migrated to 110 kD by SDS-PAGE was confirmed to react with monoclonal anti-human calpastatin antibody in immunoblotting. IgG antibodies to calpastatin were detected in 22 of 48 sera (46%) from patients with RA, whereas only 20% (5/25), 11% (2/19) and 13% (2/15) of sera from SLE, SSc and PM/DM had IgG anti-calpastatin antibodies, respectively. IgM antibodies were also found in 40% (19/48) of RA and 12% (3/25) of SLE patients but not detected in sera from patients with other rheumatic diseases. IgA antibodies were found in only one RA and one SLE serum. In RA, 7 of 48 sera (15%) had IgM antibodies alone, but all SLE sera with IgM antibodies had IgG antibodies. Thus, anti-calpastatin autoantibodies were detected by using the native human calpastatin. Although these autoantibodies were found in patients with various rheumatic diseases, they were present in RA patients at the highest frequency. In particular, the presence of IgM antibodies appeared to be more specific in RA patients.