More Selective Removal of Myeloperoxidase‐Anti‐Neutrophil Cytoplasmic Antibody From the Circulation of Patients With Vasculitides Using a Novel Double‐Filtration Plasmapheresis Therapy

Our aim was to investigate the removal of myeloperoxidase‐anti‐neutrophil cytoplasmic antibody (MPO‐ANCA) from the circulation of patients with vasculitides by double‐filtration plasmapheresis (DFPP) using various primary separator and secondary separator combinations. Nineteen patients diagnosed with vasculitides positive for serum MPO‐ANCA were enrolled and received 56 sessions of DFPP. One patient received three sessions of DFPP using MPS07 (the primary filter)/EC50W (the secondary filter), nine patients received 27 sessions of DFPP using MPS07/EC20W, and the other nine patients received 26 sessions of DFPP using EC50W/EC20W. The sieving coefficients (SC) of albumin, immunoglobulin (Ig)A, IgG and IgM were measured, as well as the reduction ratio in plasma protein concentrations and MPO‐ANCA titer after a single session of DFPP. The MPS07 filter was well permeable for all the above‐mentioned plasma proteins; the EC50W and EC20W filters were permeable for albumin and IgG, less for IgA and IgM. During DFPP using MPS07/EC50W, the reduction ratio of IgG was much lower than IgM and IgA (30.5 ± 9.0% vs. 89.7 ± 5.4% and 61.7 ± 14.8%). During DFPP using MPS07/EC20W, the decline in IgM, IgA, and IgG was 94.2 ± 3.1%, 96.2 ± 2.3%, and 64.7 ± 21.0%, respectively. During DFPP using EC50W/EC20W, the decline in IgM, IgA, and IgG was 2.8 ± 12.9%, 90.9 ± 4.4%, and 43.5 ± 13.8%, respectively. The percentage reduction in MPO‐ANCA titer after a single session of DFPP using EC50W/EC20W was 34.6 ± 14.3%. DFPP using EC50W/EC20W filters may be more selective for the removal of pathogens such as IgG, with subsequently effective reduction of serum ANCA titer.     

Immunoglobulin serum levels in very low birth weight infants treated with different intravenous preparations

Summary Parenteral human immunoglobulin (IVIG) administration is widely used in low birth weight (LBW) infants for prevention and therapy of neonatal infection. In previous studies, IVIG preparations containing IgG and low IgM concentrations were commonly used. In this study we compare immunoglobulin serum levels in two groups of healthy preterm infants receiving prophylactically standard IVIG (Sandoglobulin, 0.1 mg/kg IgM) or IgM-enriched IVIG (Pentaglobin, 30 mg/kg IgM). Immunoglobulin levels were assayed by rate nephelometry at birth and at 3, 5, 7, and 14 days after birth. The two groups of patients were matched for gestational age (31±2.3 weeks), birth weight (1320±340 g), and serum IgG (4.1±1.9 g/l) and IgM (0.22±0.18 g/l) levels at birth. Significantly higher IgM levels were observed at 3 and 5 days after IgM-enriched IVIG administration (p<0.01). Higher IgG levels were attained and persisted for 2 weeks after standard IVIG administration (p<0.01). These data indicate different IgG and IgM target levels in LBW infants treated with different immunoglobulin preparations.     

Sequential Plasmapheresis and Intravenous Immunoglobulin Therapy for Refractory Myasthenia Gravis: Case Report

Immunotherapy is currently the standard therapy for myasthenia gravis (MG) although some patients may be refractory to treatment. We describe the use of sequential plasmapheresis and intravenous immunoglobulin (IVIG) therapy for treatment of advanced MG in a patient refractory to all forms of medical treatment including corticosteroids, immunosuppressants, and intermittent plasmapheresis. The patient, a 37-year-old woman with systemic lupus erythematosus (SLE), had initially responded well to treatment with high dose corticosteroids and intermittent plasmapheresis, with the duration of response ranging from 3 to 4 months. However, after 18 months of therapy, the duration of response had gradually decreased to 1 month. She responded well to a 5 day trial of plasmapheresis followed by high dose IVIG, and the duration of response increased to 6 months. The SLE activity was relatively silent during each relapse. This report indicates the potential usefulness of sequential plasmapheresis and IVIG in the treatment of patients with refractory MG and SLE.     

Immunoglobulin and IgG subclass levels in a regional pediatric cystic fibrosis clinic

The aim of this study was to report serum immunoglobulin (Ig) and IgG subclass levels in a large pediatric population with cystic fibrosis, and relate these to measures of disease severity. Total immunoglobulin levels were measured in 154 patients, and IgG subclass levels were measured in 136 patients and compared to age-related normal population data and to levels reported in previously published studies of children with cystic fibrosis. Clinical data were also collected: genotype; height, weight, and BMI standard deviation scores; FEV(1) (as percent predicted); Shwachmann-Kulczycki (S-K) and Northern chest X-ray scores; and Pseudomonas aeruginosa infection status. The clinical well-being of patients with hypo- or hyper-gammaglobulinemia was compared with age- and sex-matched control patients who had normal levels of gammaglobulin. IgG subclass levels were measured, and the results were compared with previous studies. Eleven patients had hypergammaglobulinemia (7.8% compared with 0-69% in the published literature). Patients with hypergammaglobulinemia had lower FEV(1) percent-predicted values, and worse S-K and Northern chest X-ray scores than controls. Three patients had hypogammaglobulinemia (1.9% compared with 0-10.8% in the published literature). There was no difference in any clinical parameter between controls and those with hypogammaglobulinemia. Nineteen patients (14%) had low levels of IgG1, and 40 patients (29%) had low levels of IgG2. The low percentage of patients with abnormally high immunoglobulin levels probably reflects the improved respiratory status of today's children with CF. The low percentage of those with low IgG probably reflects better nutritional status. The finding of worse lung function and clinical scores in patients with hypergammaglobulinemia agrees with the published literature. The high percentage of patients with low IgG2 was unexpected and was not previously reported. The clinical significance of this in patients with CF is unknown.     

A Case Report of Efficiency of Double Filtration Plasmapheresis in Treatment of Goodpasture's Syndrome

Goodpasture's syndrome is characterized by pulmonary hemorrhage, rapid progressive glomerulonephritis and the presence of anti‐glomerular basement membrane (anti‐GBM) antibodies. Here, we report a case of Goodpasture's syndrome that we treated with double filtration plasmapheresis (DFPP) combined with immunosuppression therapy. The patient was a 32‐year‐old man with the main complaints of low‐grade fever, general fatigue and dyspnea. The clinical diagnosis was renal‐pulmonary syndrome based on pulmonary hemorrhage on chest X‐ray, rapid progressive renal insufficiency, and elevated C‐reactive protein (CRP). Goodpasture's syndrome was diagnosed because the patient was negative for MPO‐ANCA and PR3‐ANCA, and positive for anti‐GBM antibodies. Renal biopsy showed crescentic glomerulonephritis. Hemodialysis, immunosuppression therapy (methylprednisolone and cyclophosphamide) and DFPP were performed. Anti‐GBM antibodies were followed pre‐ and post‐DFPP, and removal efficiency, cost performance and complications were evaluated. The antibody levels were 121 and 84 EU/mL before and after the first DFPP procedure, respectively, giving a removal efficiency of 24%. Subsequently, the removal efficiencies were 52%, 55% and 60% after the second, third and fourth DFPP procedures. For comparison, the immunoglobulin G (IgG) removal efficiencies were 53%, 57%, 60% and 55% after the four respective DFPP procedures; therefore, the removal efficiencies were similar for anti‐GBM antibodies and IgG in all except the first DFPP procedure. The serum anti‐GBM antibody and IgG concentrations decreased from pre‐ to post‐DFPP, indicating that DFPP may be an effective therapeutic approach in Goodpasture's syndrome.     

Double Filtration Plasmapheresis in the Treatment of Antineutrophil Cytoplasmic Autoantibody Associated Vasculitis With Severe Renal Failure: A Preliminary Study of 15 Patients

Our aim was to investigate the clinical efficacy of double filtration plasmapheresis (DFPP) in the treatment of antineutrophil cytoplasmic autoantibody‐(ANCA) associated vasculitis (AAV) with severe renal involvement. Fifteen AAV patients who had severe renal failure (median SCr 5.6(IQR 5.2–9.0) mg/dL) and needed initial renal replacement therapy (RRT) were treated with DFPP and immunosuppressive therapy. Two plasma volumes were processed during each DFPP session. The changes of serum ANCA and renal function were investigated. After the DFPP treatment for three to five sessions, serum MPO‐ANCA level decreased from 250.0 ± 86.9 RU/mL to 70.5 ± 64.7RU/mL (P = 0.00), with a median reduction rate of 67.6%. Eleven patients (73.3%) no longer needed from RRT 3 months after DFPP treatment, while another four patients remained on dialysis. During the follow up for median 10 (IQR 6–24) months, SCr level decreased to normal in one patient, one patient progressed into ESRD. The 1 year renal survival rate was 62.9%. Five (33.3%) patients were complicated with pulmonary infection. DFPP combined with immunosuppressive therapy could increase the renal recovery rate through rapidly decreasing serum ANCA levels for AAV patients with severe renal failure, but its clinical efficacy and impact on long‐term renal survival require further studies.     

Plasmapheresis Followed by Intravenous Immunoglobulin in Presensitized Patients Awaiting Thoracic Organ Transplantation

Abstract: Four highly sensitized patients awaiting thoracic organ transplantation were treated immediately preceding transplantation with 1 plasmapheresis and infusion of high dose intravenous immunoglobulin (IVIG). All 4 underwent successful surgery and have had minor to no rejection episodes over a range from 5 1/2 to 12 months. All panel reactive antibodies (PRA) were dithiotheitol (DTT) resistant, and 1 patient had IgG specific alloantibodies to a donor alloantigen. All 4 patients had positive donor cross matches prior to transplantation, and 3 of the 4 patients remained PRA negative for up to 9 months after allografting. Possible mechanisms of this therapy include inhibition of proliferating alloreactive B cells or suppression by antiidiotypic antibodies. Further study is warranted.—     

A case report of the efficacy of apheresis for refractory autoimmune thrombocytopenia in a patient with systemic lupus erythematosus associated hemolytic anemia

Autoantibodies against platelets are found in patients with autoimmune thrombocytopenic purpura (AITP) as well as in thrombocytopenia associated with systemic lupus erythematosus (SLE). The high titer of platelet associated immunoglobulin G (PA IgG) suggests the presence of antibodies against platelets. Platelet associated antibodies are thought to play a major role in the pathogenesis of autoimmune thrombocytopenia. There is a possibility that double filtration plasmapheresis (DFPP) is effective in removing the antibodies against platelets from the peripheral blood. It is suggested that DFPP may reinforce the efforts of the conventional treatment, especially high-dose intravenous immunoglobulin therapy (IVIg). DFPP was performed for severe thrombocytopenia on a SLE patient with high PA IgG value, refractory to the conventional therapy including corticosteroid therapy and IVIg. The patient underwent three sessions of DFPP combined with IVIg and the corticosteroid therapy immediately before the initiation of IVIg. The severe thrombocytopenia improved drastically after the combination treatment, accompanied with the decrease of the PA IgG titer. It was suggested that DFPP combined with corticosteroid and IVIg was effective for severe autoimmune thrombocytopenia on SLE patients refractory to the conventional therapies.     

Clinical evaluation of titration of hepatitis C virus core antibody and its subclasses

Abstract Titrations of anti-hepatitis C core (anti-HCc) immunoglobulin G (IgG) antibodies and its subclasses were studied in 90 patients with acute and chronic hepatitis C virus (HCV) infection, including 27 patients who underwent interferon (IFN) therapy. The positivity rates for each anti-HCc subclass were as follows: 95.2% for IgG1, 12.0% for IgG2, 69.9% for IgG3 and 19.3% for IgG4. The total anti-HCc IgG titre correlated well with the IgG1 titre, indicating that IgG1 was the main virus-specific IgG. Changes of IgG1 production mainly contributed to fluctuations of the anti-HCc IgG titre and corresponded well to positivity for HCV-RNA during and after IFN therapy. IgG3 was detected prior to IgG1 during the early phase of acute hepatitis in some cases and also appeared with relapse after IFN therapy. The serial assay of anti-HCc subclasses showed the patients' humoral immune response to HCV infection, and might be useful for evaluation of anti-viral immunity influenced by IFN therapy.     

Immune thrombocytopenia and Fc receptor-mediated phagocyte function

Summary The response to intravenous immunoglobulin treatment (IVIG) is thought, in part, to be due to blockade of Fc receptor for IgG in the mononuclear phagocyte system (MPS). We have studied this by measuring splenic clearance of heat-damaged and IgG antibody-coated red cells in immune thrombocytopenic patients receiving IVIG. Clearance of heat-damaged red blood cells (HDRBC) labelled with technetium 99MM was measured in eight patients before and after a 5-day infusion of IVIG. In six of the eight there was an enhanced clearance of HDRBC post IVIG. Clearance studies were performed in eight rhesus-D-positive patients using autologous red cells coated with anti-D and labelled with^99MTc. The time taken for the radioactivity at 3 min to fall to 50% (T 1/2) was calculated. The (T 1/2) increased in seven of the eight patients from a mean of 78.5 min to 137.1 min, a prolongation of 74.6%. In addition, we have examined the effect of IVIG on Fc-mediated phagocytosis by neutrophils. Platelet phagocytosis by patients' neutrophils was measured using opsonized autologous platelets in nine patients. There was a marked reduction in platelet phagocytosis as measured by formazan production in all patients at day 4–5 when compared with the preinfusion value, and in half of these this reduction was still evident at further studies, 1 week after the end of the infusion period. The platelet count rose in parallel with the fall in platelet phagocytic ability of the neutrophils, reaching a peak at 7 days post infusion, and fell with the recovery of phagocytic function in weeks 2 and 3. These findings suggest that IVIG has a marked effect on Fc-mediated phagocytosis.     

A Case Report of Double‐Filtration Plasmapheresis for the Treatment of Age‐related Macular Degeneration

An 85‐year‐old man with dry type age‐related macular degeneration (AMD) in his right eye and a disciform scar in his left eye received double‐filtration plasmapheresis (DFPP) for the treatment of his right eye. The protocol for plasmapheresis followed the Multicenter Investigation of Rheopheresis for AMD (MIRA) trial and consisted of four pulses of paired sessions of plasmapheresis with a two‐day interval within 10 weeks. The pre‐DFPP best corrected visual acuity (BCVA) for the right eye was 6/15 (0.4). Six months after DFPP treatment, the BCVA of the right eye was 6/10 (0.6) and remained unchanged at the 12th month; however, comparison of the right eye fundus picture, fluorescein angiogram, and optical coherence tomography of the macular area before and 6 and 12 months after plasmapheresis revealed no discernable changes. The per‐session and per‐course clearance rates were highest for IgM (63.8% and 90.8%) and lowest for albumin (11% and 15.4%). No plasmapheresis‐related complications, such as hypotension, hemolysis or infection, occurred. Thus, DFPP treatment can provide effective treatment for dry type AMD with minimal side‐effects.     

Relationship between pancreatic and/or extrapancreatic lesions and serum IgG and IgG4 levels in IgG4-related diseases

OBJECTIVE: We aimed to investigate the relationship between the number of involved organs or regions and serum immunoglobulin G (IgG) and immunoglobulin G4 (IgG4) levels. METHODS: The number of pancreatic and/or extrapancreatic lesions and serum IgG and IgG4 levels were examined by groups in 46 patients with IgG4‐related diseases at diagnosis prior to the initiation of steroid treatment: group A (one region involved, n = 7), group B (two regions involved, n = 11), group C (three regions involved, n = 12), group D (four regions involved, n = 9) and group E (five to seven regions involved, n = 7). RESULTS: Both serum IgG and IgG4 levels increased with the number of inflamed regions. Mean serum IgG levels were 15.11, 18.65, 20.92, 23.29 and 30.98 g/L while the mean IgG4 levels were 3.99, 4.70, 4.70, 9.86 and 16.49 g/L in group A, B, C, D and E, respectively. Regression analysis also suggested that IgG4 was positively correlated with the number of regions involved. Additionally, serum IgG4 was higher in patients with multiple lesions when accompanied by sclerosing sialadenitis. CONCLUSION: Patients having IgG4‐related disease with high serum IgG and IgG4 levels should be systematically examined for involved lesions.     

Efficacy of intravenous gammaglobulin therapy in chronic refractory polymyositis and dermatomyositis: an open study with 20 adult patients.

PURPOSE: Polymyositis and dermatomyositis are inflammatory muscular diseases of unknown cause. Many interventions are available to treat patients with these conditions including corticosteroids, immunosuppressive drugs, plasmapheresis, and total body irradiation. However, these therapies are not always effective, and they may be associated with certain serious side effects. An attempt was made to evaluate the efficacy of polyvalent intravenous immunoglobulin (IVIG) in patients with polymyositis or dermatomyositis refractory to traditional treatment. PATIENTS AND METHODS: Twenty patients (16 women and 4 men; mean age 43 [16 SD] years), 14 with chronic refractory polymyositis and six with dermatomyositis, received high doses of IVIG because of the failure of traditional treatments (prednisone [19], methotrexate [10], azathioprine [6], cyclophosphamide [3], cyclosporine [3], chlorambucil [1], plasmapheresis [8], lymphopheresis [1], and total body irradiation [1]). In one patient with positive results on picornavirus serologic testing, IVIG was the first treatment choice. IVIG therapy was given with prednisone in 15 patients, with methotrexate in six patients, and with plasmapheresis in one patient. There were no changes in treatment in the 2 months before the introduction of IVIG therapy and no increases in dose during this treatment. Preparations of polyvalent human intravenous gammaglobulins with increased intact immunoglobulin G were used. Thirteen patients received 1 g/kg daily for 2 days each month, and seven patients received 0.4 g/kg daily for 5 days each month. The mean duration of treatment was 4 months. RESULTS: Clinical assessment, which consisted of the measurement of proximal muscle power, and biochemical studies were carried out before each treatment period. Significant clinical improvement was noted in 15 of the 20 patients. Mean muscle power estimated for the 20 patients before and after IVIG therapy was statistically significantly reduced (p less than 0.01). Eighteen patients showed biochemical improvement, and two patients with normal initial serum creatine kinase levels showed clinical improvement. Mean creatine kinase levels for the 20 patients during IVIG therapy showed a statistically significant decrease from the first IVIG perfusions (p less than 0.01). Side effects of IVIG therapy were noted in four patients; however, these effects were mild. During IVIG therapy, steroid doses were significantly reduced from the second or the third IVIG infusion (p less than 0.05). CONCLUSION: IVIG is an efficacious new therapy for polymyositis and dermatomyositis and should play a role in the treatment of these diseases, replacing or reducing steroid and immunosuppressive medications.     

A Study of the Efficacy of Plasmapheresis for the Treatment of Drug Induced Toxic Epidermal Necrolysis

Abstract: The efficacy of plasmapheresis for the treatment of toxic epidermal necrolysis (TEN) in our patient and related reports in the literature were examined. The patient, a 41-year-old female, was diagnosed as having drug (Sedes-G [isopropylantipyrin, arylisopropylacetou-reid, and phenacetinum]) induced TEN. Upon admission to our hospital, extensive corticostroid therapy was initiated. After 6 days, because more than 90% of the patient's body surface was affected by TEN, it was concluded that the patient was unresponsive to corticosteroid therapy. Double filtration plasmapheresis (DFPP) was therefore begun. After 2 sessions of DFPP, extensive reepithelial-ization rapidly occurred, and after 3 sessions of DFPP, the improvement was dramatic. The patient's condition had almost healed during 1 month's hospitalization. It has been reported in the literature that 22 patients with drug induced TEN have been treated with plasmapheresis. The mortality rate of 23 patients, including our patient, was 17.4%. The rate of effectiveness of plasmapheresis on drug induced TEN is 82.6%. It appears that some kind of necro-lytic factors were removed by the plasmapheresis. This suggests that plasmapheresis may be an effective treatment for drug induced TEN.     

Serum immunoglobulin G4 associated with number and distribution of extrapancreatic lesions in type 1 autoimmune pancreatitis patients

Background and Aim: Type 1 autoimmune pancreatitis (AIP) is characterized by the increase of serum immunoglobulin (Ig)G4 and abundant IgG4 plasma cell infiltration in the pancreas and various extrapancreatic lesions (EPL), which are proposed as IgG4‐related disease. We assessed the correlation between serum IgG4 and the number of EPL, and the association between serum IgG4 and the distribution of EPL in type 1 AIP patients. Methods: Serum IgG4 was measured in 35 type 1 AIP patients and 71 non‐AIP patients. The clinical characteristics and distribution of eight EPL were determined in 35 type 1 AIP patients. Results: Serum IgG4 in type 1 AIP was significantly higher than in non‐AIP (P < 0.001). A total of 33 patients had EPL among 35 patients with type 1 AIP (94.3%). There was a significant correlation between serum IgG4 and the number of EPL (ρ = 0.75, P < 0.001). Further, to assess the association between serum IgG4 and the distribution of EPL, type 1 AIP patients were divided into two groups: as abdominal localized EPL and systemic EPL. Both serum IgG4 and total numbers of EPL in systemic EPL were remarkably higher than those in abdominal localized EPL. Serum IgG4 cut‐off value was 346 mg/dL to distinguish between abdominal localized EPL and systemic EPL according to the receiver–operator characteristic curve data. Conclusions: Our findings indicated that serum IgG4 was useful in both the diagnosis of type 1 AIP and the detection of systemic EPL. Our finding may help the concept and diagnostic criteria of IgG4‐related disease with type 1 AIP.     

In vitro comparison of the complement-scavenging capacity of different intravenous immunoglobulin preparations

Background and Objectives  Complement inhibition is considered important in the mechanism of action of intravenous immunoglobulin (IVIG) in a number of inflammatory and autoimmune disorders. The capacity of different IVIG preparations to 'scavenge' activated C3 and thereby inhibit complement activation was assessed by a new in vitro assay.
Materials and Methods  Diluted human serum as a complement source, with or without addition of different concentrations of IVIG, was incubated in microtitre plates coated with heat-aggregated human IgG. Complement scavenging was measured by detecting reduced C3 binding and determining fluid phase C3b–IgG complex formation. Complement activation induced by the IVIG preparations was measured as C5a formation.
Results  All IVIG preparations exhibited a dose-dependent inhibition of C3b deposition, correlating strongly with binding of C3b to fluid-phase IgG, but the extent of complement scavenging varied considerably between different IVIG preparations. At an IVIG concentration of 0·9 mg/ml, the inhibition of C3b deposition ranged from 72 ± 16% to 22 ± 4·1%. The reduction of C3b deposition on the complement-activating surface was not due to IVIG-induced complement activation in the fluid phase, as shown by the low C5a formation in the presence of serum.
Conclusion  In vitro analysis allows comparison of the complement-inhibitory properties of IVIG preparations. The extent of complement scavenging varies between the products.     

Ability to Remove Immunoglobulins and Antiganglioside Antibodies by Double Filtration Plasmapheresis in Guillain-Barré Syndrome: Is It Equivalent to Plasma Exchange?

Abstract: The value of plasma exchange (PE) in Guillain-Barré syndrome (GBS) is well established. In Japan, patients with GBS and related diseases often receive double filtration plasmapheresis (DFPP) as well as PE. No comparative trials between PE and DFPP, however, have been conducted. We compared their abilities to remove immunoglobulins and antiganglioside antibodies to find out whether DFPP is equivalent to PE. The ability to remove immunoglobulins and antiganglioside antibodies was compared between PE and DFPP using plasma samples from 41 patients with GBS and related diseases before and after each treatment session. The ability of DFPP to remove both IgGs and antiganglioside IgG antibodies were significantly inferior to those of PE. There is a less theoretical basis for selecting DFPP as the first choice of plasmapheresis for GBS and related disorders.—     

Cryofiltration in the Treatment of Cryoglobulinemia and HLA Antibody‐Incompatible Transplantation

Cryofiltration is a technique in which plasma is separated from blood and chilled, leading to the formation of “cryogel”, a composite of heparin, fibronectin, fibrinogen, immunoglobulins, and other proteins. This is retained by further filtration and plasma is returned to the patient. There may be a role for cryofiltration in the treatment of cryoglobulinemia or where the application of other forms of plasmapheresis or immunoadsorption is limited. Five patients received six courses of cryofiltration. Two patients had cryoglobulinemia and three were treated before HLA antibody‐incompatible renal transplantation. The treatment was associated with few adverse effects, and it was possible to treat up to 120 mL/kg plasma per session. There was a good clinical response in four patients. One patient was switched back to double filtration plasmapheresis (DFPP) because cryofiltration seemed to remove HLA antibodies less effectively, but the other two transplants have excellent function. In the cryoglobulinemia patients there was excellent clearance of cryoglobulins during each treatment (mean decrease of 78.2 (SD 14.1)% per treatment). Compared with DFPP, fewer immunoglobulins were removed and the mean percentage reductions in immunoglobulin G per treatment were 36.0 (4.0)% for cryoglobulinemia and 59.2 (2.5)% for DFPP (P < 0.01), with respective mean plasma volumes of 64.2 (10.3) and 71.1 (6.8) mL/kg treated. Cryofiltration offers a treatment choice in patients with cryoglobulinemia and in those who may not be able to tolerate high‐volume DFPP. The technique used in the patients described here was less effective than DFPP; however, use of an alternative fractionator and treatment of higher plasma volumes may enhance the efficiency of cryofiltration.     

A longitudinal evaluation of anti‐FVIII antibodies demonstrated IgG4 subclass is mainly correlated with high‐titre inhibitor in haemophilia A patients

The development of inhibitory antibodies against factor VIII (FVIII) (inhibitor) is the major complication in haemophilia A patients. The FVIII‐binding antibodies development comprises a polyclonal immunoglobulin (Ig) G response. Recent studies showed strong correlation between the presence of neutralizing anti‐FVIII antibodies (inhibitors) and IgG4 subclass. The aim of this study was to evaluate anti‐FVIII IgG subclasses in haemophilia A patients with inhibitor both in a cross‐sectional and in a longitudinal analysis. Inhibitors were determined by Nijmegen–Bethesda assay. Anti‐FVIII IgG subclasses were performed by ELISA, and samples from 20 healthy individuals were used to validate the test. We studied 25 haemophilia A patients with inhibitor, previously treated exclusively with plasma‐derived FVIII concentrates or bypassing agents. The IgG subclasses distributions were evaluated in two groups of patients classified according to inhibitor response. IgG1 and IgG4 antibodies were most prominent in haemophilia A patients with inhibitors when compared with IgG2 and IgG3. This study reports for the first time the behaviour of FVIII‐binding IgG1 and IgG4 subclasses in a longitudinal analysis, in a clinical setting, of high‐response inhibitor haemophilia A patients, showing the correlation of IgG4 and the inhibitor titres. In spite of being considered a non‐pathologic antibody subclass with anti‐inflammatory properties in other situations, IgG4 is correlated with the presence of high‐titre inhibitor in the haemophilia setting. The comprehension of the IgG4 role in immune response may be crucial to establish the process for designing specific tolerance to FVIII.     

选择性血浆分离器行双重血浆置换对抗中性粒细胞胞质抗体清除的研究

目的：选择性血浆分离器行双重血浆置换(DFPP),观察其对髓过氧化物酶型抗中性粒细胞胞质抗体(MPO-ANCA)清除。方法：15例临床诊断血管炎且血清MPO-ANCA阳性患者共接受44例次DFPP治疗。DFPP分三种方式,即MPS07/EC50W组合(血浆分离器MPS07作一级滤器,血浆成分分离器EC50W作二级滤器);MPS07/EC20W组合(MPS07及EC20W分别作一、二级滤器);EC50W/EC20W组合(EC50W及EC20W分别作一、二级滤器)。治疗剂量为处理2倍血浆容量,每次治疗补充人体白蛋白30～40g。其中1例患者采用MPS07/EC50W组合治疗3次,9例患者采用MPS07/EC20W组合治疗27次,余5例患者采用EC50W/EC20W组合治疗14次。DFPP采用间断弃浆方式,在弃浆前再使用生理盐水800 ml使二级滤器中蛋白再滤过后再弃浆。测定三种滤器对血浆白蛋白、IgA、IgG及IgM的筛选系数(SC),及单次治疗前后血浆这些蛋白下降百分率,MPO-ANCA下降百分率,及清除指数。结果：MPS07血浆分离器能滤过血浆中多数蛋白,SC＞0.6;EC50W滤器能滤过血浆白蛋白及IgG,滤过IgA略差,IgM则不能滤过(SC 0.06),EC20W滤器只能部分滤过白蛋白及IgG,滤过IgA更少,IgM不能滤过(SC 0.03)。三种方式DFPP单次治疗对血浆白蛋白影响不明显,MPS07/EC50W组合对血浆IgM清除最明显,IgA其次,IgG相对较差;MPS07/EC20W组合对三种免疫球蛋白清除都较好,尤以IgM及IgA更好;EC50W/EC20W组合对IgA及IgG清除较好,而对IgM无影响。采用EC50W/EC20W组合治疗单次IgG下降率达(43.5±13.8)％,MPO-ANCA滴度下降率(34.6±14.3)％,IgG清除指数0.47±0.15,MPO-ANCA清除指数0.34±0.09,白蛋白清除指数0.29±0.08。弃浆前采用生理盐水冲滤器可使废液中IgG/白蛋白比例提高24.2％。结论：对于清除以IgG为主的治疗,应选择EC50W/EC20W滤器组合方式以提高IgG清除的选择性,避免其他大分子物质丢失,有效降低血清MPO-ANCA滴度。