A B S T R A C T The metabolism ofthe fifth component of complement (C5), and its relationship to metabolism of the third component of complement (C3), has been studied in normal subjects and patients by simultaneous administration of radioiodine labeled C5 and C3. In seven normal subjects the fractional catabolic rate of C5 ranged from 1.5 to 2.1% of the plasma pool/h and extravascular/intravascular distribution ratio from 0.22 to 0.78, these values being similar to those obtained for C3, and synthesis rate from 71 to 134 ,g/kg per h. In patients with complement activation the increase in fractional catabolic rate of C5 was nearly always less than that of C3. The data also showed that there was increased extravascular distribution of C3 and C5 in most patients and considerable extravascular catabolism of both proteins in some. However, there were differences in metabolic parameters between patients with different types of complement activation. In patients with systemic lupus erythematosus, fractional catabolism and extravascular distribution of C3 and C5 were both increased, and there was marked extravascular catabolism of both proteins. There was increased fractional catabolism and extravasctular distribution of C3 in patients with mesangiocapillary nephritis and (or) partial lipodystrophy, and fractional catabolisim of C5 was also increased in three of six studies although distribution of C5 was always within the normal range; however, in two patients with nephritic factor in their serum fractional catabolism of C5 was normal despite markedly increased C3 turnover, suiggesting that in patients with alterna- INTRODUCTIONThe fifth component of complement (C5)1 is the major component of the final common pathway of complement activation-the membrane attack complex C5-9. The cleavage of C5-the final enzymatic step in the complement sequence-yields a larger fragment, C5b, which binds C6-9 to formn the membrane attack complex, and a smaller fragment, C5a, which has anaphylatoxic and chemotactic activity.The suibunit structure of C5 is very similar to that of the third component (C3) (1), and this is reflected by the similarity of the C3 and C5 cleaving enzymes (convertases) which are generated after activation of complement by the classical or alternative pathways. Thus the classical pathway C3 convertase, C4b2a, binds the major cleavage fragment of C3, C3b, to become a C5 convertase C423b.The mechanism of formation and composition of the alternative pathway C3 and C5 convertases has been the subject of mtuch recent investigation. Upon activation of the alternative pathway C3b is generated and interacts with factors B and D (D cleaving Factor B) in the C3b feedback or amplifica-

most of these the inheritance appears to be that of an X-linked codominant trait.A rapid and precise immunoelectrophoretic assay of TBC has recently been developed using a monospecific antiserum to TBC. The assay has been used to identify three families with hereditary elevation of TBC, comprising sixteen affected individuals. The mean serum thyroxine (T,) in these individuals was 2 14 nmol (normal range 60-130 nmol/l) although all were clinically euthyroid, and absolute free thyroxine values were within the normal range. Mean serum TBC in affected males ( n = 4) was 42.3mg/l, and in females ( n = 12) 26.3mg/l (normal range 6-16mg/l). This sex difference in TBC levels is predictable on the basis of an X-linked dominant inheritance, with higher levels in hemizygous males than in heterozygous females (Lyon hypothesis). Serum thyroxine binding prealbumin was reduced by approximately 25% in those with elevated TBG concentration.In several individuals, the calculated free thyroxine index (FTI) was in the thyrotoxic range. A comparison of T3 uptake results with serum TBC concentration showed that the uptake test underestimated TBC concentration when this was abnormally high, resulting in abnormal FTI results.A correction of the T4 concentration based on actual TBC concentration is better than FTI in correcting for binding protein abnormalities: EFFECT OF HAEMODIALYSIS ON THYROID FUNCTION P. DANDONA, D. NEWTON and M. M . PLAITS Royal Hospital, Sheffield(Introduced by N. MCINTYRE) Thyroid function has been studied in seventy-three patients with chronic renal failure. The patients studied have been divided arbitrarily into the fotlowing four groups: those studied before the institution of haemodialysis (group I), those dialysed for less than 6 months (group II), those dialysed for between 6 months and 3 years (group 111) and those dialysed for longer than 3 years (group IV). The mean serum albumin, protein binding, PBI, total T4 and FTI were significantly greater in patients in group I1 than those in group I, the increase in mean PBI, T4 and FTI being similar to that of albumin concentrations and protein binding. The mean serum T4 concentration and FTI in patients of group 111 were significantly lower than those in group I1 and greater than those in group IV, although the mean serum albumin, protein binding and PBI were not significantly different in the groups 11, Ill and IV. Serum T, concentration was low in all patients in whom it was measured in all four groups.The incidence of subnormal thyroid hormone concentrations was as follows: four out of twelve patients (33%) in group IV had subnormal PBI, T4 and FTI; in group Ill, three out of thirty-one patients (9%) had low PBI, T4 and FTI; in group 11, one patient had low FTI whereas FTI was normal in all patients in group 1.Serum TSH concentration was high normal in patients of group 1 and I1 and supra normal in patients of groups 111 and IV. TRH induced TSH increase in serum TSH concentration was subnormal in patients of groups I and I1 and absent in patients of groups I...