Altered follicular regulatory T (Tfr) and helper T (Tfh) cell subsets are associated with auto‐antibody levels in microscopic polyangiitis patients

2021 ◽  
Author(s):  
Yan Long ◽  
Jinghong Feng ◽  
Yinting Ma ◽  
Yuanyuan Sun ◽  
Lijuan Xu ◽  
...  
Keyword(s):  
Microscopic Polyangiitis ◽  
Antibody Levels ◽  
Auto Antibody

scholarly journals Use of porcine factor VIII in the treatment of patients with acquired hemophilia

Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1513-1520 ◽  
Author(s):  
AE Morrison ◽  
CA Ludlam ◽  
C Kessler
Keyword(s):  
Factor Viii ◽  
Acquired Hemophilia ◽  
First Line Therapy ◽  
Human Factor Viii ◽  
Plasma Factor ◽  
Inhibitor Level ◽  
Clinical Responses ◽  
Bleeding Episodes ◽  
Antibody Levels ◽  
Auto Antibody

Abstract Data have been collected from 47 centers in Europe and North America on the treatment with porcine factor VIII concentrate of 74 acute bleeding episodes in 65 patients with acquired hemophilia. The median initial anti-human factor VIII auto-antibody inhibitor level was 38 Bethesda unit (BU)/mL (range 1.2 to 1,024) whereas that against porcine was 1 BU/mL (range 0 to 15). The mean initial dose of porcine factor VIII infused was 84 IU/kg, which increased the plasma factor VIII:C activity by 0.85 IU/mL. Therapy was continued for a mean of 8.5 days during which time the average number of infusions was 11. Objective clinical responses were rated as good or excellent in 78% of recipients. Side effects were uncommon; only one patient experienced a severe anaphylactic reaction necessitating the discontinuation of porcine FVIII therapy. After therapy, no increase in the median level of anti- human FVIII or anti-porcine antibody was noted in the group as a whole, although 13 patients showed individual increases in either anti-human or anti-porcine antibody levels or both of more than 10 BU/mL. Of the 7 patients who subsequently rebled, 5 were successfully re-treated and 2 did not respond to further porcine factor VIII treatment. Porcine factor VIII is safe and clinically effective treatment for bleeding episodes associated with acquired hemophilia and should be considered as first-line therapy for patients whose acquired anti-factor VIII:C antibody cross-reacts with porcine factor VIII:C at low levels.

scholarly journals PARP inhibition in atherosclerosis and its effects on dendritic cells, T cells and auto-antibody levels

2011 ◽  
Vol 16 (8) ◽  
pp. 367 ◽  
Author(s):  
C Erbel ◽  
J Achenbach ◽  
M Akhavanpoor ◽  
TJ Dengler ◽  
F Lasitschka ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Parp Inhibition ◽  
Antibody Levels ◽  
Auto Antibody

scholarly journals Use of porcine factor VIII in the treatment of patients with acquired hemophilia

Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1513-1520 ◽  
Author(s):  
AE Morrison ◽  
CA Ludlam ◽  
C Kessler
Keyword(s):  
Factor Viii ◽  
Acquired Hemophilia ◽  
First Line Therapy ◽  
Human Factor Viii ◽  
Plasma Factor ◽  
Inhibitor Level ◽  
Clinical Responses ◽  
Bleeding Episodes ◽  
Antibody Levels ◽  
Auto Antibody

Data have been collected from 47 centers in Europe and North America on the treatment with porcine factor VIII concentrate of 74 acute bleeding episodes in 65 patients with acquired hemophilia. The median initial anti-human factor VIII auto-antibody inhibitor level was 38 Bethesda unit (BU)/mL (range 1.2 to 1,024) whereas that against porcine was 1 BU/mL (range 0 to 15). The mean initial dose of porcine factor VIII infused was 84 IU/kg, which increased the plasma factor VIII:C activity by 0.85 IU/mL. Therapy was continued for a mean of 8.5 days during which time the average number of infusions was 11. Objective clinical responses were rated as good or excellent in 78% of recipients. Side effects were uncommon; only one patient experienced a severe anaphylactic reaction necessitating the discontinuation of porcine FVIII therapy. After therapy, no increase in the median level of anti- human FVIII or anti-porcine antibody was noted in the group as a whole, although 13 patients showed individual increases in either anti-human or anti-porcine antibody levels or both of more than 10 BU/mL. Of the 7 patients who subsequently rebled, 5 were successfully re-treated and 2 did not respond to further porcine factor VIII treatment. Porcine factor VIII is safe and clinically effective treatment for bleeding episodes associated with acquired hemophilia and should be considered as first-line therapy for patients whose acquired anti-factor VIII:C antibody cross-reacts with porcine factor VIII:C at low levels.

scholarly journals Partial Protection From Lupus-Like Disease by B-Cell Specific Type I Interferon Receptor Deficiency

2021 ◽  
Vol 11 ◽  
Author(s):  
Emma J. Keller ◽  
Neeva B. Patel ◽  
Madeline Patt ◽  
Jane K. Nguyen ◽  
Trine N. Jørgensen
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Immune Cell ◽  
Type I ◽  
Type I Ifns ◽  
B Cell Survival ◽  
Complex Deposition ◽  
Antibody Levels ◽  
Auto Antibody

Systemic lupus erythematosus (SLE) is an autoimmune disease that can present with many different permutations of symptom presentation. A large subset of SLE patients have been shown to present with elevated interferon stimulated gene (ISG) expression, and Type I IFNs (IFNαβ) have been shown to drive disease in murine models through global IFNα Receptor (IFNAR) knockouts. However, the disease contribution of distinct immune cell subsets in response to constitutively increased levels of IFNαβ is not fully understood. We utilized a B-cell specific IFNAR knockout (BΔIFNAR) on the B6.Nba2 spontaneous-lupus background to determine the contribution of IFNαβ stimulated B cells in disease. We found that IFNαβ signaling in B cells is driving increased splenomegaly, increased populations of activated B cells, and increased populations of germinal center (GC) B cells, memory B cells, and plasma blasts/cells, but did not affect the development of glomerulonephritis and immune-complex deposition. IFNAR expression by B cells also drove production of anti-chromatin IgG, and anti-dsDNA and -nRNP IgG and IgG2C auto-antibody levels, as well as increased Bcl2 expression, affecting GC B cell survival in B6.Nba2 mice.

Rituximab Maintenance Therapy for Granulomatosis with Polyangiitis and Microscopic Polyangiitis

2011 ◽  
Vol 39 (1) ◽  
pp. 125-130 ◽  
Author(s):  
CLAIRE ROUBAUD-BAUDRON ◽  
CHRISTIAN PAGNOUX ◽  
NADINE MÉAUX-RUAULT ◽  
ANNE GRASLAND ◽  
ABDELKADER ZOULIM ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Granulomatosis With Polyangiitis ◽  
Microscopic Polyangiitis ◽  
Controlled Trial ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Maintenance Infusion ◽  
Randomized Controlled ◽  
Rituximab Maintenance ◽  
Induction Regimen ◽  
Antibody Levels

Objective.To evaluate the efficacy compared to the relapse risk and tolerance of systematic rituximab (RTX) infusions as maintenance therapy for patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), who entered remission taking conventional immunosuppressants or RTX.Methods.A retrospective study of the main clinical characteristics, outcomes, and RTX tolerance of patients who had received ≥ 2 RTX maintenance infusions in our center, regardless of induction regimen, between 2003 and 2010.Results.We identified 28 patients [4 MPA and 24 GPA; median age 55.5 yrs (range 18–78); 17 (60%) males] who received a median of 4 (range 2–10) RTX maintenance infusions, with median followup of 38 months (range 21–97) since diagnosis or last flare. None experienced a RTX infusion-related adverse event; 15 patients (among the 21 with available data) had hypogammaglobulinemia (predominantly IgM) prior to their last RTX maintenance infusion; 3 had infectious events (1 cutaneous abscess, 1 otitis, 1 fatal H1N1 flu). Two patients suffered pulmonary relapses shortly before a planned RTX maintenance infusion (both had increased antineutrophil cytoplasmic antibody levels and 1 had CD19+ lymphocyte reconstitution).Conclusion.Rituximab maintenance therapy was well tolerated but did not completely prevent relapses and persistent “grumbling” disease. These preliminary results remain to be confirmed by a randomized controlled trial currently in progress.

Cardiac Specific Auto-Antibody Levels are not Increased after Bypass Surgery

1995 ◽  
Vol 89 (s33) ◽  
pp. 39P-39P
Author(s):  
JH Goldman ◽  
V Sentilnathan ◽  
R Warraich ◽  
MK Baig ◽  
M Gould ◽  
...  
Keyword(s):  
Bypass Surgery ◽  
Antibody Levels ◽  
Auto Antibody

Prevalence and Induction of Circulating Antibodies against Recombinant Staphylokinase

1994 ◽  
Vol 71 (01) ◽  
pp. 129-133 ◽  
Author(s):  
P J Declerck ◽  
S Vanderschueren ◽  
J Billiet ◽  
H Moreau ◽  
D Collen
Keyword(s):  
Intravenous Administration ◽  
Human Subjects ◽  
Microtiter Plates ◽  
Staphylococcus Aureus Bacteremia ◽  
Alternative Agent ◽  
Antibody Titers ◽  
Potential Alternative ◽  
Circulating Antibodies ◽  
Low Levels ◽  
Antibody Levels

SummaryStreptokinase (SK) is a routinely used thrombolytic agent but it is immunogenic and allergenic; staphylokinase (STA) is a potential alternative agent which is under early clinical evaluation. The comparative prevalence of antibodies against recombinant STA (STAR) and against SK was studied in healthy subjects and their induction with intravenous administration in small groups of patients.Enzyme-linked immunosorbent assays, using microtiter plates coated with STAR or SK and calibration with affinospecific human antibodies, revealed 2.1 to 65 μg/ml (median 11 μg/ml) anti-STAR antibodies and 0.9 to 370 μg/ml (median 18 μg/ml) anti-SK antibodies (p <0.001 vs anti-STAR antibodies) in plasma from 100 blood donors, with corresponding values of 0.6 to 100 μg/ml (median 7.1 μg/ml) and 0.4 to 120 μg/ml (median 7.3 μg/ml), respectively, in 104 patients with angina pectoris. Three out of 17 patients with Staphylococcus aureus bacteremia had significantly increased anti-STAR antibody levels (150, 75 and 75 μg/ml), and STAR neutralizing activities (2.2, 3.6 and 4.1 μg STAR neutralized per ml plasma, respectively). In 6 patients with acute myocardial infarction, given 10 mg STAR intravenously over 30 min, median anti-STAR antibody levels were 3.5 μg/ml at baseline, 2.9 μg/ml at 6 to 8 days and 1.2 μg/ml at 2 to 9 weeks, with median corresponding titers of STAR neutralizing activity at 2 to 9 weeks of 42 μg/ml plasma. Conversely, in 5 patients treated with 1,500,000 units SK over 60 min, median anti-SK antibodies increased from 2.9 μg/ml at baseline to 360 μg/ml at 5 to 10 days, with corresponding median SK neutralizing activities of 13 μg/ml. Antibodies against STAR did not cross-react with SK and vice versa.Plasma from human subjects contains low levels of circulating antibodies against recombinant staphylokinase, and intravenous administration of this compound boosts antibody titers. These antibodies do however not cross-react with streptokinase, whereby the use of these two immunogenic thrombolytic agents would not be mutually exclusive.

Management of Haemophilia A with Antibodies - The Effect of Combined Treatment with Factor VIII, Hydrocortisone and Cyclophosphamide

1985 ◽  
Vol 54 (04) ◽  
pp. 776-779 ◽  
Author(s):  
U Hedner ◽  
L Tengborn
Keyword(s):  
Factor Viii ◽  
Combined Treatment ◽  
Factor Ix ◽  
Treatment Schedule ◽  
High Antibody ◽  
Anamnestic Response ◽  
Short Intervals ◽  
Low Responders ◽  
Antibody Levels ◽  
High Responders

SummaryImmune tolerance has by several methods been induced in haemophiliacs with antibodies. A conversion of “high responders” into “low responders” was previously reported after repeated moderate factor IX doses over periods of 7-10 days in combination with cyclophosphamide and steroids in two patients with haemophilia B and inhibitors. This paper reports similar results in a heamophilia A patient by giving factor VIII, cyclophosphamide, and steroids during relatively short periods of time (7-8 days). The anamnestic response markedly decreased already following the first treatment and never exceeded a level of 1 u/ml (˜ 3 BU/ml) even when boosted with ordinary factor VIII doses for only 3 days. It is concluded that the markedly decreased secondary antibody response is most probably the result of factor VIII given at short intervals (twice a day) for periods of up to about one week when given in combination with cyclophosphamide and steroids. The same effect may be achieved by other methods. The treatment schedule suggested in the present paper is, however, simple and avoids long periods of high antibody levels. Furthermore, the total factor VIII dose used is lower than suggested in most other treatment schedules, which makes the treatment substantially less expensive.

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