672

negative ANA. Of the 5 patients with positive ANAs, 4 became "negative" during the ensuing 8-12 months, while all were taking L1regularly. 1 patient, after 9 months on LI, has an intermittently weakly speckled pattern of ANA positivity. The frequency of a positive ANA in the Indian patients with arthropathy is therefore identical to that in the Canadian patients, all of whom, before initiation of Ll, had been erratically compliant or non-compliant

a

with desferrioxamine. There is a background of ANA positivity in patients with thalassaemia major. Mehta and colleagues’ statement that Ll "can cause serious immune alterations" is unsupported. The nature and value of the "detailed immunological testing" suggested is unclear. The second consideration is the evidence of a lupus-related death in

Fig 2-Competitive inhibition immunoassay

with SLE

serum

and cofactor. . = presence, 0 =absence of 10

0 g/ml

human cofactor

We conclude that ACA in SLE serum do not recognise cofactor cardiolipin alone, but recognise either the complex of cardiolipin and cofactor or novel epitopes on the cofactor that appear after binding to cardiolipin and phospholipids.

or

2nd Department of Internal Medicine, Chiba University School of Medicine, 1-8-1 Inohana, Chiba 280, Japan

TAKAO KOIKE

Immunology Laboratory, Shoyu Co. Ltd, Japan

EIJI MATSUURA

Yamasa

EN, Pierangeli S, Barquinero J, Ordi-Ros J. Anticardiolipin antibodies and binding of anionic phospholipids and serum protein. Lancet 1990; 336: 505-06. 2. Harris EN, Pierangeli S. What is the "true" antigen for antiphospholipid antibodies? Lancet 1990; 336: 1505. 3. Galli M, Comfurius P, Maassen C, et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990; 335: 1544-47. 4. Bevers EM, Galli M. &bgr;2-glycoprotein I for binding of anticardiolipin antibodies to cardiolipin. Lancet 1990; 336: 952-53. 5. Matsuura E, Igarashi Y, Fujimoto M, Ichikawa K, Koike T. Lancet 1990; 336: 177-78.

the patient described. Although reporting a classic presentation, Mehta et al fail to emphasise the well-documented association death sudden cardiovascular and between pulsed at doses to or less than this patient equal methylprednisolone received.’ This has been reported as late as 10 days after methylprednisolone administration, frequently in patients with pre-existing heart disease.2 The statement that cardiac dysfunction was unlikely to be due to iron overload is unsupported: in an 18-year-old transfusion-dependent individual with a history of "suboptimal desferrioxamine", significant cardiac dysfunction would not be unexpected.3 Several groups, including the investigators in Bombay, are carefully evaluating the use of this and related compounds.,, None of them has suggested to the lay press or in any other form that LI should now replace desferrioxamine, despite the latter’s expense and toxicity/ in the treatment of iron load. ICSGOIC tried to convey this message to the media of India at the time of the meeting, and continues to condemn the indiscriminate use of any chelating agent. Department of Haematology/Oncology, Prince of Wales Children’s Hospital, Randwick, NSW 2031, Australia

VASILI BERDOUKAS

1. Harris

Antinuclear antibodies in

patients taking L1

SIR,—The International Collaborative Study Group on Oral Iron Chelators (ICSGOIC), of which I am chairman, was formed in November, 1989, and consists of 56 clinicians and scientists, all experienced in the administration of iron chelators. Having attended the International Society for Oral Iron Chelation meeting in Bombay, November, 1990,am writing to clarify some of the issues raised by the finding of joint pains and positive tests for antinuclear antibodies (ANA) in patients receiving LI, which were discussed in detail at that meeting. I would also like to comment on Dr Mehta and colleagues’ report (Feb 2, p 298) on a fatal case of systemic lupus erythematosus (SLE) in a patient taking L1. At the meeting, arthropathy, with or without positive tests for ANA and antibodies to histones, was reported in 15 of 36 patients receiving Ll at one centre. The arthropathy, which has not been observed at this frequency in any other centre, and which has not been seen at all by several investigators, remains unexplained. However, it emerged at the meeting that there was evidence of a high frequency of hepatitis B positive blood administration in Bombay transfusion centres, in contrast to those in Canada, the UK, Switzerland, and the Netherlands. Symptomatic arthropathy can complicate chronic hepatitis. 7 of the 15 patients with complaints of arthropathy had a positive ANA. Of 21 patients without arthropathy, 9 had a positive ANA. Of 29 patients who are not receiving LI, 3 had a positive ANA. These findings are compatible with those reported at the same meeting by the Toronto investigators. Of 12 Canadian patients tested before administration of L 1, 5 had a positive test for ANA, 2 of these also had a positive rheumatoid factor (RF), and 3 had a positive RF with

1. Erstad BL. Severe cardiovascular adverse effects in association with acute, high dose corticosteroid administration. DICP 1989; 23: 1019-23. 2. Gardiner PVG, Griffiths ID. Sudden death after treatment with pulsed methylprednisolone. Br Med J 1990; 300: 125. 3. Wolfe LC, Olivieri NF, Sallan DL, Propper RD, Freedman MH, Nathan DG. The prevention of cardiac disease by subcutaneous deferoxamine in patients with thalassemia major. N Engl J Med 1985; 312: 1600-03. 4. Kontoghiorghes GJ, Bartlett AN, Hoffbrand AV, et al Long-term trial with the oral chelator l,2-dimethyl-3-hydroxypyrid-4-one (L1). Br J Haematol 1990; 76: 295-300. 5. Tondury P, Kontoghiorghes GJ, Ridolfi-Luthy A, et al. L1 (1,2-dimethyl-3hydroxypynd-4-one) for oral iron chelation in patients with beta-thalassaemia major. Br J Haematol 1990; 76: 550-53. 6. Olivieri NF, Koren G, Hermann C, et al. Comparison of oral iron chelator L1 and desferrioxamine in iron-loaded patients. Lancet 1990; 336: 1275-79. 7. Porter JB, Huehns ER The toxic effects of desferrioxamine. Baillière’s Clin Haematol 1989; 2: 459-74.

Lipoprotein(a) reduction by N-acetylcysteine SiR,—In their report, Dr Gavish and Dr Breslow (Jan 26, p 203) describe reductions in plasma Lp(a) concentrations after Nacetylcysteine (NAC) treatment in two patients. In-vitro NAC reduced the linking disulphide bonds between apo(a) and Lp(a) and led to dissociation of the complex. Clinical trials are clearly warranted, but NAC may influence atherogenesis by other mechanisms. Low-density lipoprotein (LDL) that has been oxidatively modified by endothelium, arterial smooth muscle cells, or monocytes-macrophages can bind to macrophage scavenger receptors (acetyl LDL receptors), and this unregulated uptake may lead to foam cell formation.In addition, oxidatively modified LDL may promote atherogenesis by its cytotoxic properties, by inhibition of growth factor production by endothelial cells, or by recruitment and retention of monocytes-macrophagesThe cellmediated oxidative modification of LDL is initiated by the reactive oxygen species, superoxide.3 Evidence suggests that arterial smooth muscle cells produce superoxide and modify LDL by a process dependent on specialised cellular uptake of L-cystine, with

Antinuclear antibodies in patients taking L1.

672 negative ANA. Of the 5 patients with positive ANAs, 4 became "negative" during the ensuing 8-12 months, while all were taking L1regularly. 1 pati...
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