Antineutrophil antibodies

Immune-mediated mechanisms of clozapine-induced agranulocytosis have been reviewed in the context of agranulocytosis in a 46-year-old woman (140). Immune and toxic mechanisms have also been explored in patients taking clozapine, three who developed agranulocytosis, seven who developed neutropenia, and five who were asymptomatic. There was no evidence of antineutrophil antibodies in the blood of patients shortly after an episode of clozapine-induced agranulocytosis, and an antibody mechanism... 

A direct toxic effect of vancomycin and/or an immune-mediated mechanism (antineutrophil antibodies, sensitized lymphocjrtes) have been discussed. 

In the last decade, extensive evidence has gathered suggesting involvement of Kupffer cell-mediated inflammatory reactions in Gin-induced liver injury. It is known that Gin leads to activation of Kupffer cells resulting in secretion of proinflammatory cytokines such as tumor necrosis factor (TNF)-a. Increased levels of TNF-a leads to neutrophilic infiltration and cytotoxicity in the liver. Depletion of both Kupffer cells by glycine and gadolinium chloride and of neutrophils by antineutrophil antibodies protect from... 

Davies DJ, Moran JE, Niall JF, Ryan GB. Segmental necrotising glomerulonephritis with antineutrophil antibody Possible arbovirus aetiology BMJ 1982 285 606. 

Antineutrophil antibodies, possibly generated by reaction of nitrenium ions with neutrophil proteins resulting in hapten formation, may also be involved in the etiology of clozapine-induced neutropenia. There is likely to be an immune component since the reaction occurs more quickly and is more severe on rechaUenge of patients who have developed clozapine-induced neutropenia. 

The inflammatory response in UC is propagated by atypical type 2 helper T cells that produce proinflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF).7 As discussed previously, a genetic predisposition to UC may partially explain the development of excessive colonic and rectal inflammation. The finding of positive perinuclear antineutrophil cytoplasmic antibodies (pANCA) in association with the human leukocyte antigen (HLA)-DR2 allele in a large percentage of patients with UC supports this theory.4,12... 

Ulcerative colitis Leukocytosis, decreased hematocrit/hemoglobin, elevated erythrocyte sedimentation rate (ESR), guaiac-positive stool, (+) perinuclear antineutrophil cytoplasmic antibodies (pANCA up to 70% of patients)... 

Shapiro, L.E., Uetrecht, J., and Shear, N.H. Minocycline, perinuclear antineutrophilic cytoplasmic antibody and pigment The biochemical basis, J. Amer. Acad. Dermatol., 45, 787, 2001... 

Pelletier, F. et al, Minocycline-induced cutaneous polyarteritis nodosa with antineutrophil cytoplasmic antibodies, Em J. Dermatol., 13, 396, 2003. 

Ototoxicity has rarely been attributed to antithyroid drugs (13). In one case progressive bilateral sensorineural hearing loss attributed to propylthiouracil was associated with myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) (14). 

Of 14 cases of suspected drug-induced liver disease presenting to a gastroenterology department over a 3-year period, one was thought to be related to thiamazole, with a hepatitic pattern of liver function tests in a 39-year-old woman 6 days after the start of therapy recovery was swift and complete (48). Delayed cholestatic hepatitis without antineutrophil cytoplasmic antibodies has been reported (49), and there have been fatal cases of hepatic necrosis (SEDA-21, 438) (7). 

Acute pancreatitis and parotitis without antineutrophil cytoplasmic antibodies has been attributed to thiamazole (53). 

Antithyroid drugs, especially propylthiouracil, can be associated with the development of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis, often manifesting as renal disease. Atypical presentations, with pulmonary capillaritis (58) and lupus-like syndrome (59), have been described in individual cases. Furthermore, two cases of vasculitis have been associated with carbimazole, one presenting with eosinophilic granulomatous vasculitis localized to the stomach (60) and another with p-ANCA positive vasculitis causing simultaneous acute renal insufficiency and massive pulmonary hemorrhage (61). 

Slot MC, Links TP, Stegeman CA, Tervaert JW. Occurrence of antineutrophil cytoplasmic antibodies and associated vasculitis in patients with hyperthyroidism treated with antithyroid drugs a long-term followup study. Arthritis Rheum 2005 53(1) 108-13. 

Gao Y, Ye H, Yu F, Guo XH, Zhao MH. Anti-myeloper-oxidase IgG subclass distribution and avidity in sera from patients with propylthiouracil-induced antineutrophil cytoplasmic antibodies associated vasculitis. Clin Immunol 2005 117(l) 87-93. 

Choi HK, Merkel PA, Walker AM, Niles JL. Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis prevalence among patients with high titers of antimyeloperoxidase antibodies. Arthritis Rheum 2000 43(2) 405-13. 

Sera N, Yokoyama N, Abe Y, Ide A, Usa T, Tominaga T, Ejima E, Kawakami A, Ashizawa K, Eguchi K. Antineutrophil cytoplasmic antibody-associated vasculitis complicating Graves disease report of two adult cases. Acta Med Nagasaki 2000 45 33-6. 

Otsuka S, Kinebuchi A, Tabata H, Yamakage A, Yamazaki S. Myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis following propylthiouracil therapy. Br J Dermatol 2000 142(4) 828-30. 

Matsubara K, Nigami H, Harigaya H, Osaki M, Baba K. Myeloperoxidase antineutrophil cytoplasmic antibody positive vasculitis during propylthiouracil treatment successful management with oral corticosteroids. Pediatr Int 2000 42(2) 170-3. 

Antineutrophil cytoplasmic antibody (ANCA)-positive cutaneous leucocytoclastic vasculitis associated with antithyroid therapy in Graves disease. Australas J Dermatol 1998 39(2) 96-9. 

Gunton JE, Stiel J, Caterson RJ, McElduff A. Clinical case seminar anti-thyroid drugs and antineutrophil cytoplasmic antibody positive vasculitis. A case report and... 

Miller RM, Darben TA, Nedwich J, Savige J. Propylthiouracil-induced antineutrophil cytoplasmic antibodies in a patient with Graves disease and a neutrophilic dermatosis. Br J Dermatol 1999 141(5) 943-4. 

Wada N, Mukai M, Kohno M, Notoya A, Ito T, Yoshioka N. Prevalence of serum anti-myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) in patients with Graves disease treated with propylthiouracil and thiamazole. Endocr J 2002 49(3) 329-34. 

Katayama K, Hata C, Kagawa K, Noda M, Nakamura K, Shimizu H, Fujimoto M. Diffuse alveolar hemorrhage associated with myeloperoxidase-antineutrophil cytoplasmic antibody induced by propylthiouracil therapy. Respiration 2002 69(5) 473. 

Hong SB, Lee MH. A case of propylthiouracil-induced pyoderma gangrenosum associated with antineutrophil cytoplasmic antibody. Dermatology 2004 208(4) 339-41. 

Harper L, Chin L, Daykin J, Allahabadia A, Heward J, Gough SC, Savage CO, Franklyn JA. Propylthiouracil and carbimazole associated-antineutrophil cytoplasmic antibodies (ANCA) in patients with Graves disease. Clin Endocrinol (Oxf) 2004 60(6) 671-5. 

ACE = angiotensin-converting enzyme ANA = antinuclear antibody ANCA = antineutrophil cytoplasmic antibody BUN = blood urea nitrogen CBC = complete blood count ELISA = enzyme-Mnked immunoassay assay ESR = erythrocyte sedimentation rate FTA-ABS = fluorescent treponemal antibody absorption HLA = human lymphocyte antigen MHA-TP = micro-hemagglutination-7re/ OMew pallidum-, PPD = purified protein derivative RPR = rapid plasma reagin VDRL = venereal disease reference laboratory. 

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