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症例は26歳，女性.発熱および肝機能障害にて入院.抗生剤治療不応の弛張熱と皮疹を特徴とし，肝生検などにより白血病や悪性リンパ腫などの疾患を除外して成人発症Still病と診断した.急性肝不全を呈し，ステロイドパルス療法によりいずれの臨床症状も軽快したが，ステロイドの減量によりすぐに再燃した．更に血球減少を呈するマクロファージ活性化症候群（macrophage activation syndrome，MAS）に移行した．シクロスポリンおよび静注用リポ化ステロイドの投与を開始したところMAS症状は改善し，第41病日に退院した．成人発症Still病に合併したMASにはシクロスポリンおよびリポ化ステロイドの治療が有用であった．

ファブリー病に対して酵素補充療法（ERT）が実用化され，アガルシダーゼアルファ，アガルシダーゼベータの2剤が使用可能である．しかし，透析患者に対してのデータは少ない．特に，アガルシダーゼアルファに関しては血液透析（HD）中投与のデータがないため，HD中投与の可否につき薬物動態の検討を行った．【症例】46歳，男性．26歳時に脳梗塞を発症し，ファブリー病と診断．平成18年7月に血液透析導入，11月よりアガルシダーゼベータによるERTを開始したが，投与関連反応高度のため，平成19年4月よりアガルシダーゼアルファに薬剤を変更．疼痛発作，発汗障害，下痢などの自覚症状はERT開始後1年程度で改善し，心機能の悪化も認めていない．本例に対しHD中，非HD中にERTを行い，薬物動態を検討したが，HD中投与と非HD中投与で，血漿中の酵素活性に差は認めなかった．【まとめ】アガルシダーゼアルファはベータと同様にHD中に投与可能である．また，ERTにより，症状の改善のみならず，心機能維持効果が示唆された．透析患者に対しても，ERTの継続は重要であり，ベータとアルファでの臨床効果の差は認められず，ベータが投与困難な症例に対しアルファへ変更し投与を継続することは効果的であると思われる．

To elucidate the molecular mechanism of glomerular events in lupus nephritis, we performed genome-wide mRNA expression analysis of glomeruli microdissected from lupus mice. MRL/lpr mice (12-week-old) were orally given vehicle or prednisolone (10 mg/kg per day) for 4 weeks. Renal histology of MRL/lpr mice revealed mesangial proliferative glomerulonephritis with cellular infiltration of macrophages, T cells, and neutrophils. We identified 567 upregulated genes in MRL/lpr glomeruli compared to control congenic mice. Those included complement components, adhesion molecules, chemokines and their receptors, and molecules related to antigen presentation. Over 130 genes were considered preferentially or exclusively expressed in hematopoietic cell lineages possibly reflecting leukocytes accumulation. Of note is the finding that chemokines and chemokine receptors (CCL3, CCL4, CCL5, CXCL9, CXCL10, CXCL11, CXCL16, CCR5, CXCR3, and CXCR6) that are related to T helper 1 (Th1) cells accumulation were up-regulated concomitantly with increased expression of Ebi3, a subunit of IL-27 that plays a role in Th1 predominance. These changes were accompanied by increased mRNA expression of many genes that were inducible by Th1 cytokine interferon-γ. Prednisolone markedly attenuated glomerular lesion and leukocyte influx parallel with the reduction of enhanced gene expression. The present study shows additional evidence supporting glomerular Th1 cells accumulation and their role. Our data also provide an important resource in seeking new therapeutic targets to lupus nephritis.Supplemental table: available only at http://dx.doi.org/10.1254/jphs.FP0071337 Keywords:: lupus nephritis, chemokine, Th1, interferon-γ, IL-27

Long-term effects of Ca antagonist and ACE inhibitor on renal function in hypertensive patients with chronic renal failure of IgA nephropathy were studied. Both Ca antagonists and ACE inhibitors were equally effective in reducing blood pressure.

We conducted a prospective multicenter study to assess early changes in the dynamics of bone metabolism in patients with systemic connective tissue diseases following commencement of high-dose glucocorticoid therapy and the benefits of early treatment with bisphosphonate and vitamin D analogue. The subjects of this randomized controlled trial were 106 female patients with systemic connective tissue diseases treated for the first time with glucocorticoids at doses equivalent to prednisolone ≥20 mg/day (age ≥ 18 years). One week after initiation of glucocorticoid therapy, patients were randomly assigned to treatment with alfacalcidol at 1 μg/day (n = 33), alendronate 35 mg/week (n = 37), and alfacalcidol plus alendronate (n = 36). The primary endpoints were changes in lumbar spine bone density at 6 months of treatment and the frequency of bone fracture at 12 months. Commencement of glucocorticoid therapy was associated with a rapid and marked bone resorption within 1 week. The combination of alfacalcidol and alendronate administered after the first week of glucocorticoid therapy halted the pathological processes affecting bone metabolism, increased bone density, and reduced the incidence of bone fracture over a period of 12 months. Taken together, the use of the combination of alfacalcidol and alendronate improved bone metabolism, increased bone density, and significantly reduced the incidence of bone fracture during 1-year high-dose glucocorticoid therapy.

A 57-year-old woman presented with a purpuric rash. Cryoglobulins were detected, and a skin biopsy showed leukocytoclastic vasculitis. The alanine aminotransferase level was 119 IU/L, and the platelet count 63,000/mm3. The hepatitis B virus (HBV) DNA was 6.4 log10 copies/mL and became negative by week 6 of entecavir therapy. The antiphosphatidylserine-prothrombin complex antibody (anti-PS/PT) was 390-510 U/mL, and decreased to 69 U/mL at week 24, after cryoglobulin had become negative and the rash resolved. Among 20 HBV-infected patients without extrahepatic manifestations, low titers of anti-PS/PT were detected in 8 (40%). Clinical characteristics were similar in patients with or without anti-PS/PT. Low titers of anti-PS/PT in chronic hepatitis B have little clinical significance, whereas high titers may promote cryoprecipitate formation.

Anti-angiogenic compound (TNP-470) inhibits mesangial cell proliferation in vitro and in vivo. Growth factors, especially basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) are known to play key roles in the pathogenesis of mesangial proliferative glomerulonephritis. TNP-470 (AGM-1470), a potent anti-angiogenic compound, has anti-growth factor properties and inhibits the activation of cyclin-dependent kinase (cdk) 2 and phosphorylation of RB protein. We investigated whether TNP-470 could suppress growth factor induced mesangial cell proliferation in vitro and experimental model of mesangial proliferative glomerulonephritis in vivo. TNP-470 inhibited potently PDGF- and bFGF-stimulated proliferation of rat mesangial cells in vitro (IC50 = 50 pg/ml). In anti-Thy 1.1 glomerulonephritis, high dose use of TNP-470 (20 mg/kg/day) markedly suppressed mesangial cell proliferation and mesangial matrix expansion on day 6; however, mesangiolysis remained. Low dose use of TNP-470 (10 mg/kg/day) moderately inhibited mesangial cell proliferation and mesangial matrix synthesis, and induced appropriate glomerular healing on day 14 in anti-Thy 1.1 glomerulonephritis. Thus, TNP-470 potently inhibits growth factor-induced proliferation of mesangial cells in vitro, and mesangial cell proliferation and extracellular matrix expansion in anti-Thy 1.1 glomerulonephritis in vivo. These results suggest a novel therapeutic potential of TNP-470 in mesangial proliferative glomerulonephritis.

SUMMARY 1. We examined preproendothelin-1, ETA and ETb receptor mRNA levels in aortic endothelial and smooth muscle cells from cyclosporine (CyA)-induced hypertensive rats using the reverse transcription polymerase chain reaction method. 2. Aortic endothelial preproendothelin-1 mRNA expression was about 1.5-fold higher, while that of ETB receptor mRNA was markedly decreased in CyA-treated rats compared with those in controls. 3. The expression of ETA receptor mRNA in smooth muscle cells from CyA-induced hypertensive rats was increased about two-fold over that in cells from control animals. 4. Thus, increased endothelial preproendothelin-1, and ETa receptor mRNA levels in smooth muscle cells, which are concomitant with the decrease in ETB receptor mRNA levels in endothelium, may contribute to CyA-induced hypertension in rats.

To clarify the role of PDGF A-chain in hypertensive vascular hypertrophy of spontaneously hypertensive rats (SHRs), we studied levels of PDGF A-chain gene expression and transcription factors related to the gene in vascular smooth muscle cells (VSMCs) of SHRs in vivo. RNase protection assay and in situ hybridization showed that PDGF A-chain mRNA levels in VSMCs of SHRs were twofold higher than in those of normotensive Wistar-Kyoto rats. Gel retardation assays showed that levels of Sp1 and AP-2 in VSMCs of SHRs were twofold more abundant than in those of Wistar-Kyoto rats. Treatment with four pharmacologically different species of antihypertensive drugs for 2 wk decreased the levels of both PDGF A-chain mRNA and Sp1, but not AP-2 level in VSMCs of SHRs with regression of aortic hypertrophy, indicating that increases in levels of both PDGF A-chain mRNA and Sp1 in VSMCs of SHRs were associated with high blood pressure. These results suggest that high blood pressure is a stimulus which upregulates PDGF A-chain gene expression in VSMCs of SHRs, resulting in an autocrine enhancement in hypertensive vascular hypertrophy, and that the activation of the gene may be mediated through increases in Sp1 in these cells.

To examine the regulation of angiotensin receptors in vascular smooth muscle cells, we studied the effects of antihypertensive drugs on angiotensin type 1A (AT1A) receptor gene expression in aortic smooth muscle cells (ASMCs) from spontaneously hypertensive rats (SHRs) using both ribonuclease protection assay and reverse-transcription polymerase chain reaction. An increase in AT1A receptor gene expression in ASMCs of SHRs was induced by treatment with an angiotensin converting enzyme inhibitor (enalapril) for 2 weeks and 4 weeks, but not by other types of antihypertensive drugs such as alpha-blocker (doxazosin), alpha, beta-blocker (arotinolol), Ca antagonist (nicardipine) or vascular smooth muscle relaxant (hydralazine). Since all antihypertensive drugs lowered the blood pressure of the rats almost equally, our results suggest that AT1A receptor gene expression in ASMCs of SHRs may be regulated by the vascular renin-angiotensin system.

1. Na+ influx into cultured vascular smooth muscle cells (VSMC) obtained from spontaneously hypertensive rats (SHR) and from Wistar-Kyoto rats (WKY) was measured. Na+ influx via the Na+/H+ exchange system was measured as the rate of 22Na+ influx into cultured VSMC sensitive to ethylisopropylamiloride (EIPA), a specific inhibitor of the exchange system. 2. The total 22Na+ influx rate in SHR was significantly higher than in WKY (6.08 +/- 0.16 vs 4.13 +/- 0.09 nmol/min per mg protein; P less than 0.001; n = 14). The EIPA (1 X 10(-4) mol/L)-sensitive 22Na+ influx rate in SHR was significantly higher than that in WKY (4.32 +/- 0.27 vs 2.17 +/- 0.14 nmol/min per mg protein; P less than 0.001; n = 14). There was no difference in EIPA-insensitive 22Na+ influx between SHR and WKY. The EIPA-sensitive 22Na+ influx rate into VSMC was significantly decreased in SHR but not in WKY by the addition of 1 X 10(-4) mol/L 1-(5-isoquinoline-sulfonyl)-methylpiperazine (H-7), an inhibitor of protein kinase C (PK-C). 3. These results suggest that the increase in Na+ influx in SHR may be due to elevation of the Na+/H+ exchange activity, and possible involvement of PK-C in the increased Na+/H+ exchange activity in VSMC from SHR.

A 56-year-old man with bilateral hearing impairment who had taken betamethasone combined with dexchlorpheniramine maleate for 7 years to treat chronic sinusitis developed a dry cough after discontinuing this medication and was diagnosed with asthma, and after which he sensed impaired bilateral hearing. Based on the presence of numerous eosinophilic leukocytes in otorrehea, we made a diagnosis of eosinophilic otitis media, and he was prescribed predonisolone to control the asthma, but discontinued it on his own. He then developed fever, maniphalanx stiffness, testicular pain, and facial hyperesthesia, eruptions, and the lower-limb numbness. The detection of a positive serum reaction for MPO-ANCA and evaluated of eosinophilic leukocyte levels yielded a definitive diagnosis of CSS, for which the man was treated with predonisolone and cyclophosphamide. His symptoms were relieved, even though the onset of neutropenia, necessitated the discontinuation of cyclophosphamade administration.

Because the clinical significance of von Willebrand factor (vWF), a marker of endothelial injury, has not been well studied in adult patients with dermatomyositis (DM), we evaluated whether plasma vWF levels are useful as an index of disease activity in these patients. We measured plasma vWF antigen levels in 11 patients with active adult DM, 13 patients with inactive DM, and 18 healthy subjects using an enzyme-linked immunosorbent assay. The association of vWF level with clinical condition and muscle-derived enzyme leakage among DM patients was examined using analysis of covariance and logistic regression analysis. Furthermore, we studied the effects of treatment on the vWF antigen level. The mean vWF antigen level was significantly higher in active DM patients than in inactive DM patients and healthy subjects. Higher vWF levels were associated with clinical symptoms, such as general fatigue, fever, and muscle weakness. They were also associated with the levels of aspartate aminotransferase, alanine aminotransferase, and aldolase, but not with those of lactate dehydrogenase and creatine kinase (CK). vWF antigen was correlated with muscle enzymes except for CK. The plasma vWF levels in six patients with active DM significantly decreased after successful corticosteroid treatment. Plasma vWF level may be considered a useful marker of disease activity in adult DM patients.

We report here two interesting cases of systemic lupus erythematosus(SLE) accompanied by antiphospholipid syndrome nephropathy(APSN). These cases satisfied the criteria for SLE established by the American College of Rheumatology 1997 and also satisfied the criteria for antiphospholipid syndrome (APS) established by the Sapporo International Workshop of APS 1998. Both cases had high blood pressure with elevated plasma renin activity, proteinuria and renal dysfunction. Their biopsied renal specimens showed the characteristic findings for APSN, such as mesangial proliferation, double contours, thickening of the capillary loops, and intimal hyperplasia, but there was no evidence for immune complexes in the glomeruli, which were examined by the indirect immunofluorescence methods and the electron microscopy method. These results indicated that their renal dysfunction was caused by APSN, but not by immune complex nephritis. In addition to treatment with prednisolone, they were administered anticoagulants(warfarin, or aspirin, or heparin) for APSN and an angiotensin II receptor blocker, candesartan, for the hypertension. Subsequently, their conditions recovered with the improvement of renal function and hypertension. Our experiences suggest that anticoagulant therapy in addition to corticosteroids offers advantages in the treatment of patients with SLE accompanied by APSN and renal dysfunction.

A 20-year-old woman had polyarticular-onset type of juvenile rheumatoid arthritis with a chronic and destructive course since 6 years of age. She had developmental retardation, deformity and disability. Asymptomatic erythematous scaly plaques developed on the trunk. A skin biopsy specimen revealed psoriasis. This is the first report of psoriasis developing in a patient with juvenile rheumatoid arthritis.

Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, inhibits the synthesis of mevalonic acid and is widely used as an anti-atherosclerotic drug. The macrophage scavenger receptor (SCR), a trimeric membrane glycoprotein, is postulated to play a key role in atheroma macrophage foam cell formation. HMG-CoA reductase is involved in the control of the synthesis of glycoproteins and farnesylated proteins, including ras proteins, which are involved in the transcriptional regulation of SCR gene expression. Accordingly, we examined whether lovastatin alters the gene expression of SCRs in THP-1 cell derived human macrophages. Lovastatin (5–15 μM) caused a significant dose-related reduction in steady state levels of type-I SCR mRNA in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells. The addition of exogenous mevalonate (1 mM) completely restored the lovastatin-induced decrease of type-I SCR mRNA levels. While the addition of the isoprenoid end-product, isopentenyl adenine (50 μM), had little effect on the type-I SCR mRNA levels in lovastatin-treated cells, the addition of isoprenoid farnesol (5 μM) largely restrored the lovastatin-induced decrease of type-I SCR mRNA levels. Actinomycin D treatment showed that degradation rates of type-I SCR mRNA did not differ between the THP-1 derived cells with and without lovastatin treatment. Nuclear run-on assays showed that lovastatin markedly decreased the transcription of SCR gene in the cells. These results suggest that lovastatin inhibits the transcription of type-I SCR gene by affecting mevalonate metabolism, possibly through the farnesyl-pyrophosphate related end-product(s) in the THP-1-derived macrophages.

We examined the gene expression of angiotensin AT1A receptors in aortic endothelial cells of cyclosporine induced hypertensive rats using reverse transcribed polymerase chain reaction method. The gene expression of angiotensin AT1A receptors in aortic endothelial cells of cyclosporine induced hypertensive rats showed a two-fold increase when compared with that in normotensive control rats. These results raise a possibility that the up-regulation of endothelial angiotensin AT1A receptors participates in the pathogenesis of cyclosporine induced hypertension.

The correlation between renal histology and class specific (IgG and IgM) antibodies to double stranded DNA (dsDNA) and single stranded DNA (ssDNA) was studied by enzyme linked immunosorbent assay (ELISA) in 40 untreated patients with systemic lupus erythematosus (SLE). The levels of IgG antibodies to dsDNA were significantly higher in patients with World Health Organisation class IV nephritis than in those with class I, class II, or class III nephritis. IgG antibodies to ssDNA were higher in patients with class IV than in those with class II nephritis. IgG antibodies to dsDNA showed a close correlation with the histological activity score and the amount of electron dense deposit. IgG antibodies to ssDNA showed only a weak correlation with the renal histological activity score. IgM antibodies to dsDNA and IgM antibodies to ssDNA were not correlated with renal histological features. Patients with moderate to severe nephritis had a lower ratio of IgM antibodies to dsDNA to IgG antibodies to dsDNA than those with mild nephritis. These results indicate that the measurement of IgG antibodies to dsDNA is predictive in evaluating renal histological activity in patients with SLE.

We examined angiotensin II induced changes of inositol 1,4,5-triphosphate (Ins(1,4,5)P3) in cultured vascular smooth muscle cells from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) using a specific protein binding assay system. We observed a rapid biphasic Ins(1,4,5)P3 response, which peaked at 5 s and at 30 s after angiotensin II stimulation. At every period of time the Ins(1,4,5)P3 level of SHR was 2- to 5-fold higher than that of WKY. Thus, the Ins(1,4,5)P3 specific assay revealed a complex Ins(1,4,5)P3 response after angiotensin II stimulation and suggested the need for further investigation of the Ins(1,4,5)P3 metabolism following agonist stimulation in vascular smooth muscle cells.

A corticosteroid- and furosemide-induced excessive increase in proteinuria developed in a 34-year-old nephrotic patient with focal glomerulosclerosis. The concentration of urinary protein increased almost in parallel with that of urinary glucose. This finding indicates that corticosteroids and/or furosemide can promote the disturbance of the tubular reabsorption mechanism together with increases in glomerular permeability and glomerular filtration rate.

We performed immunopathologic studies of the pericarditis present in a patient with mixed connective tissue disease. A large number of nuclear RNP (nRNP) immune complexes (ICs) were found in the pericardial fluid, but not in the serum. The pericardial small vessels had no deposits of IgG. These results suggest that locally formed nRNP ICs were closely associated with the pathogenesis of pericarditis in this patient.

Complement activation in IgA nephropathy. Activation of alternative complement pathway is presumed to be important pathogenically in IgA nephropathy since renal biopsies usually exhibit glomerular deposition of C3 and P (properdin). Surprisingly, little is known about plasma complement activation in this disease, and the plasma C3 and C4 concentrations are usually normal or increased. We quantitated C3 activation in 202 plasmas from 81 patients with IgA nephropathy using a sensitive new assay that detects a neoantigen ((iC3b-C3d neoantigen) which appears when C3b is inactivated to iC3b, C3dg, or C3d. This assay accurately quantitates small amounts of in vivo C3 activation. The concentration of iC3b-C3d neoantigen in plasma was significantly increased, indicating C3 activation in 37% of the pediatric and 57% of the adult plasmas assayed. When data from serial determinations in the patients were analyzed, 75% of the adult and 57% of the pediatric patients had C3 activation on at least one occasion. Classical pathway activation, quantitated by C4 activation was found in 20% of the adult and 5% of the pediatric plasmas. No association was found between elevated iC3b-C3d neoantigen concentration and history of macroscopic hematuria, chronic renal insufficiency or degree of proteinuria. These studies show that complement activation can frequently be detected in the plasma of IgA nephropathy patients. However, the pathophysiologic significance of this complement activation remains to be determined.

65才男子に生じたIgGλ型骨髄腫に合併した全身性アミロイドーシスの1例を報告した。手指の感覚異常にひき続き, 口囲, 鼻前庭部などに無症候性丘疹が出現した。光顕的にはダイロン染色で真皮にアミロイドの沈着を認め, 血管周囲にもアミロイドの沈着が認められた。また, 真皮下層にアミロイド中を弾性線維が縦走する像が認められた。電顕的には表皮直下から塊状にアミロイドの沈着を認め, それを取り囲むように線維芽細胞が突起を伸ばす像が観察された。一部のアミロイド塊中には, 膠原線維や弾性線維がみられた。また, 一部の血管周囲では, アミロイド非沈着部が認められ, 必ずしも血管周囲からアミロイドが形成されていくのではないと考えられた。剖検では, 全身諸臓器にアミロイドの沈着が認められた。とくに, 心内膜下ではアミロイド中に弾性線維を認めたが, 心外膜下では認められず, アミロイド沈着に弾性線維は必ずしも必要ないと考えられた。

We studied the expression of c-myc proto-oncogene in hearts and cultured aortic smooth muscle cells of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), in order to investigate the association of the c-myc gene with cardiac hypertrophy and atherosclerosis in SHR. Transcription of the c-myc gene in hearts of SHR was higher than that of WKY at 10 weeks of age, when cardiac hypertrophy had developed in SHR. The c-myc gene expression in cultured aortic smooth muscle cells of SHR, after the addition of serum to the serum-deprived cultures, was higher than that of WKY. These results suggest that the enhanced expression of the c-myc gene in the hearts and cultured aortic smooth muscle cells of SHR may be associated with the growth control of these cells, and may play a role in the development of cardiac hypertrophy and atherosclerotic lesions in SHR.

We developed a microtiter solid-phase radioimmunoassay for quantitating C3 breakdown products (iC3b, C3dg, C3d) in human plasma with a unique monoclonal antibody specific for a neoantigen present on iC3b and C3d (MoAb 130). This monoclonal antibody reacts with a neoantigen which appears when C3b is converted to iC3b. The neoantigen is also present on the C3dg and C3d fragments derived from iC3b. The concentration of the neoantigen is elevated in the plasma of most patients with rheumatoid arthritis and systemic lupus erythematosus as compared to normal volunteers. Some patients with glomerulonephritis also had elevated concentration of the neoantigen in their plasma.

In an attempt to find a reliable method to assess fever in patients with systemic lupus erythematosus (SLE), a multifactorial analysis was applied to the routine laboratory examinations, including white blood cell count (WBC) and serum globulin fraction concentrations. During 74 febrile episodes, 49 SLE patients showed increased disease activity and the remaining 25 febrile episodes were due to intercurrent infection. The two different groups of fever episodes were clearly separated by a principal component analysis using five variables from the routine laboratory tests, including WBC, serum alpha-1, alpha-2, beta, and gamma globulins. Discriminant analysis showed that 95% of 74 febrile episodes could be correctly classified as to the cause of fever when a combination of WBC and alpha-2 globulin level was used as variables. A simple discriminant formula which we calculated was considered to be of practical use for the differentiation of the two clinical entities.

We measured alpha 2-plasmin inhibitor-plasmin complexes (PI-PC) in plasma of patients with systemic lupus erythematosus (SLE) to examine the plasminogen activation in SLE. The plasma PI-PC level in 23 patients with SLE was significantly higher than that in 18 normal subjects (P less than 0.001) and the SLE patients with nephrotic syndrome had higher plasma PI-PC levels than those without nephrotic syndrome (P less than 0.01). In addition, the plasma PI-PC level was significantly correlated with the level of plasma C3 breakdown products (iC3b/C3dg) in the patients with SLE (r = 0.53, P less than 0.01). These results suggest that plasminogen is activated in plasma of patients with SLE and that the plasminogen activation may be associated with the activation of complement in SLE.

We studied the expression of an iC3b neoantigen (iC3b-NEO) in plasma from patients with systemic lupus erythematosus (SLE), by using a monoclonal antibody specific for iC3b/C3dg/C3d, to investigate the activation of the third component of complement in SLE. The plasma iC3b-NEO level in 40 untreated patients with active SLE was significantly higher than that in 36 normal subjects (mean +/- SD 31.5 +/- 13.9 micrograms/ml versus 12.3 +/- 3.3 micrograms/ml; P less than 0.001). The plasma iC3b-NEO level was highly correlated with clinical disease activity (tau = 0.62, P less than 0.0001), and it was the parameter most closely correlated with renal histologic activity in lupus nephritis (tau = 0.52, P less than 0.0001). Also, patients with diffuse proliferative lupus nephritis had the highest levels of plasma iC3b-NEO among all World Health Organization classes of lupus nephritis (P less than 0.01). We conclude that the plasma iC3b-NEO level is strongly associated with clinical disease activity and renal histologic activity in patients with SLE, and that plasma iC3b-NEO may be a sensitive and useful measure of complement activation in SLE.

We measured U1-RNP: anti-U1-RNP immune complexes (U1-RNP ICs) in patients with mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE) to examine the clinical significance of circulating U1-RNP ICs. The level of U1-RNP ICs in 11 patients with MCTD was significantly higher than that in 22 normal subjects and there was a close correlation between the level of U1-RNP ICs and the clinical disease activity index of MCTD. In contrast, the level of U1-RNP ICs in 31 patients with SLE was not significantly higher than that in normal subjects and that was not correlated with the clinical disease activity index of SLE or the renal histologic activity index of lupus nephritis. We conclude that U1-RNP ICs are present in sera of patients with MCTD and SLE, and that the level of U1-RNP ICs may be closely associated with clinical disease activity in patients with MCTD.

We developed a solid-phase radioimmunoassay for complement (C)-fixing nuclear ribonucleoprotein (nRNP):anti-nRNP immune complexes (nRNP ICs). The assay was based on the ability of the C-fixing nRNP ICs to bind strongly to immobilized F(ab')2 anti-C3. The extent of binding was quantified by incubating the C-fixing nRNP ICs bound to anti-C3 with 125I-labeled anti-nRNP-specific IgG. The interaction between anti-C3 and C-fixing nRNP ICs was rapid, time- and concentration-dependent and sensitive over a broad range of nRNP IC concentrations in an antigen-antibody ratio of 8 : 1 (9.8-5000 ng of human aggregated IgG equivalent per ml). We found that the assay also detected an immunoreactive U1-RNP antigen in Sm : anti-Sm immune complexes but did not detect SSA : anti-SSA immune complexes. The assay was preliminary applied for serum samples obtained from patients with mixed connective tissue disease (MCTD), and elevated concentrations of nRNP immune complexes were found in 3 out of 5 patients with MCTD. This assay appears to be applicable to the detection and quantification of circulating nRNP ICs in patients with MCTD.

Serum concentrations of interferon alfa, interleukin 1, and tumour necrosis factor alpha were measured in 25 untreated patients with systemic lupus erythematosus (SLE). A close correlation was found between serum concentrations of interferon alfa and the degree of fever, while no significant correlations were found between fever and interleukin 1 or tumour necrosis factor alpha. These results suggest the possible involvement of interferon alfa in the pathogenesis of fever in SLE.

• The relationship between the renal pathologic activity of systemic lupus erythematosus (SLE) and serum lactate dehydrogenase (LDH) was examined in 28 patients with active SLE involving only the kidney. Serum levels of total LDH, LDH1, and LDH2 were significantly higher in the patients with diffuse proliferative lupus nephritis (World Health Organization class IV) than in those with milder renal disease (classes I through III and V). Total LDH levels showed good correlations with the activity index and the total pathologic score of the renal pathologic scoring system, and with the glomerular hypercellularity and overall deposits. The elevated level of LDH was mainly due to elevated levels of its isozymes LDH1 and LDH2. These results suggest that the elevation of serum LDH levels in patients with SLE reflects the renal pathologic changes due to lupus nephritis. (Arch Intern Med1986;146:548-552)