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Biomedical subjects

C G Kallenberg

Publications and source records attributed to C G Kallenberg.

At least 199 records · Page 11Linked to original sources

C-reactive protein levels during disease exacerbations and infections in systemic lupus erythematosus: a prospective longitudinal study.

We prospectively studied the value of measuring C-reactive protein (CRP) levels in patients with systemic lupus erythematosus (SLE) to distinguish between disease exacerbation and infection. During a 2 year followup of 71 lupus patients, 38 episodes of disease exacerbation and 36 episodes of infection could be analyzed. Plasma samples were obtained at least once a month. CRP levels were increased (greater than 6 mg/l) during 25 of the 38 exacerbations and during 32 of the 36 infections. Median CRP levels during infection (60 mg/l; range 1-400) were higher than during disease exacerbation (16.5 mg/l; range 1-375) (p less than 0.05). Levels of CRP rose prior to the exacerbation (p less than or equal to 0.01) and fell afterwards (p less than or equal to 0.01). During exacerbations accompanied by serositis, median levels of CRP (76 mg/l; range 2-375) were higher than during exacerbations without serositis (16 mg/l; range 1-53) (p less than 0.02). CRP levels exceeding 60 mg/l during exacerbations without serositis indicated infection in all cases. Thus, measurement of CRP in SLE is valuable to distinguish between infection and exacerbation only in the absence of serositis.

Adolescent↗

Early detection of connective tissue disease in patients with Raynaud's phenomenon.

Connective tissue diseases such as scleroderma frequently show an insidious onset. In their early stages a diagnosis of a specific CTD is hard to make, and the disorder may then be designated as "undifferentiated CTD." Raynaud's phenomenon (RP) is the first symptom in many cases and may precede the disease for many years. RP, however, is a common finding in the population, especially in young females. Thus, only a minority of patients with RP will develop a CTD. For reason of prognosis and early diagnosis and to get more insight in the initial pathophysiological processes, it is important to know which patients with RP will develop or are already evolving into a CTD. Patients referred to the clinician because of RP frequently (24-40%) show signs or symptoms of CTD, especially of scleroderma. Pulmonary function disturbances and esophageal hypomotility are asymptomatic in many cases, and should be sought for with sensitive methods. How can we distinguish patients with truly primary RP from those who will evolve into CTD (and thus should be screened for CTD and be followed)? The presence of antinuclear antibodies (ANA) and abnormalities at nailfold capillary microscopy (NCM) have proven to be early indicators of evolution into CTD, especially scleroderma and related disorders. The antigenic specificities of ANA indicate which syndrome the patient will develop, e.g., anti-CENP-B indicates the CREST-syndrome and anti-topoisomerase I diffuse scleroderma. Other factors of prognostic significance in patients with RP are age at onset and severity of RP: older age at onset and a highly severe RP represent risk factors for CTD. What do we know about the evolution of RP into CTD? Follow-up studies on patients referred because of RP have shown that some 15-20% of these patients have an insidious progress to limited cutaneous scleroderma including CREST. Risk factors have already been mentioned. From a pathophysiological point of view, studies in patients with early scleroderma have proved that microvascular changes are crucial in the disease process. These changes, demonstrated morphologically by NCM and functionally, e.g., by pulmonary function studies, are also reflected in increased levels of VIII antigen and in in vivo platelet activation. Both of these phenomena probably result from endothelial damage. There is increasing evidence that T-cells and their products are involved in vascular damage in early scleroderma. Future research should be directed to the elucidation of the target antigens for these T-cells.

Antibodies, Antinuclear↗

Renal effects of indomethacin in patients with systemic lupus erythematosus.

We evaluated the effect of indomethacin on renal function in a sodium-restricted state in control subjects and in patients with systemic lupus erythematosus (SLE) without major disease activity and with normal or only slightly impaired glomerular filtration rate (GFR). In the patients with SLE indomethacin 150 mg daily induced a fall in GFR of mean 15.8%, while effective renal plasma flow remained constant. Neither effective renal plasma flow, nor GFR changed significantly in the controls. One should be aware that nonsteroidal anti-inflammatory drugs (NSAID) may decrease GFR in SLE, also in patients without disease activity and with normal or only slightly impaired GFR. As effective renal plasma flow remained constant, it is suggested that the indomethacin-induced fall in GFR in SLE is caused by mesangial contraction.

Adult↗

Wegener's granulomatosis autoantibodies identify a novel diisopropylfluorophosphate-binding protein in the lysosomes of normal human neutrophils.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) specifically associated with Wegener's granulomatosis were found to be directed against a saline-soluble glycoprotein triplet that migrates on SDS gels as distinct bands of Mr 29,000, 30,500, and 32,000 and is present in the azurophilic granules. This antigen was specifically recognized by all cytoplasmic-staining (C)-ANCA-positive sera from patients with Wegener's disease. C-ANCA antigen bound [3H]diisopropylfluorophosphate, which indicates that it is a serine protease, but it could clearly be distinguished from the serine proteases elastase and cathepsin G. Stimulation of cytochalasin B-treated neutrophils with FMLP induced release of C-ANCA antigen. This indicates that in vivo C-ANCA might interact with the C-ANCA antigen after its release upon inflammatory stimulation. We further demonstrate that in some perinuclear staining (P-ANCA) patients' sera autoantibodies against other myeloid lysosomal enzymes can be detected, such as antimyeloperoxidase and antielastase. C-ANCA and P-ANCA thus represent a novel class of autoantibodies directed against myeloid lysosomal enzymes. The originally described Wegener-specific C-ANCA show an apparently uniform specificity for the 29,000 serine protease. In contrast, P-ANCA may recognize myeloperoxidase as well as elastase and/or other antigens.

Antibodies, Monoclonal↗

Pulmonary function in patients presenting with Raynaud's phenomenon without an underlying connective tissue disease. A prospective, longitudinal study.

Forty-two patients presenting with Raynaud's phenomenon (RP) were prospectively evaluated for pulmonary function changes over a 6-year followup period. Fifteen patients had secondary RP at presentation, 27 patients had nonsecondary RP. In the latter group, decreased pulmonary diffusing capacity (Tlco) was observed in only 2 patients (7%) whereas 9 patients with secondary RP (60%) had decreased Tlco. In the group of patients with nonsecondary RP exhibiting one or more autoantibodies, Tlco values were lower than in the group without autoantibodies (p less than 0.01). In patients with nonsecondary RP the duration of disease was correlated with the level of Tlco (r = 0.55), probably explained by a higher prevalence of truly primary RP in patients with longstanding nonsecondary RP. During followup no significant changes in pulmonary function were observed in the group with nonsecondary RP. We conclude that pulmonary function testing in patients presenting with nonsecondary RP without autoantibodies does not appear of clinical value.

Adult↗

Sequential development of antibodies to specific Sm polypeptides in a patient with systemic lupus erythematosus: evidence for independent regulation of anti-double-stranded DNA and anti-Sm antibody production.

We describe a patient with systemic lupus erythematosus who, after a disease flare, sequentially produced antibodies to specific Sm polypeptides (demonstrated by counterimmunoelectrophoresis, immunoblotting, and RNA immunoprecipitation) concomitantly with the disappearance of anti-double-stranded DNA antibodies. Immunoblotting studies revealed that antibodies to the D polypeptide appeared first, followed by antibodies to BB' and E polypeptides, respectively. Our findings suggest that antibodies to the Sm-specific polypeptides do not occur simultaneously and that the regulation of their production is independent of that of antibodies to double-stranded DNA.

Adult↗

AA amyloidosis associated with systemic lupus erythematosus.

A 54-year-old female with a 23-year history of systemic lupus erythematosus was admitted because of loss of renal function and nephrotic syndrome. Renal biopsy showed deposition of AA amyloid as demonstrated by Congo red staining and reactivity with protein AA-specific antibodies. Immune deposits were present in the mesangium and the glomerular basement membrane, but histopathological changes consistent with lupus nephritis were not detected. The rare association of systemic lupus erythematosus and amyloidosis is discussed in view of the characteristics of the acute phase reaction in systemic lupus erythematosus.

Amyloidosis↗

Arterial thrombotic manifestations in young women associated with the lupus anticoagulant.

To demonstrate the wide variety of clinical syndromes associated with the lupus anticoagulant (LAC), we report the case histories of three young females with arterial thrombosis in whom LAC was demonstrated. Two patients had a diagnosis of systemic lupus erythematosus and mixed connective tissue disease respectively; the other patient had no signs of underlying auto-immune disease. Arterial thrombotic events in young females should arouse suspicion of the presence of LAC although its pathophysiological significance is not established.

Adult↗

Immunoglobulin genes, HLA-B8/DR3, and immune responsiveness to primary immunogen and mitogens in normal subjects.

The genetic regulation of immune responsiveness by genes from two independent, highly polymorphic genetic systems, namely immunoglobulin allotypes and human leukocyte antigens (HLA), was studied in 35 healthy Caucasian volunteers. The in vivo IgG class antibody response to the primary test immunogen alpha-helix pomatia hemocyanin (HPH) was increased in subjects with the Gm1,17;..;21 haplotype compared to that of the non-Gm1,17;..;21 group. The IgM-class response tended to be higher in the former group. Levels of in vivo IgA-class-specific anti-HPH antibodies tended to be higher in the group of individuals positive for HLA-B8/DR3 than in the non-B8/DR3 group. This difference was statistically significant only in the absence of the Gm1,17;..;21 haplotype. The in vitro lymphocyte proliferative response on mitogenic stimulation with phytohemagglutinin (1 micrograms/ml) and pokeweed mitogen (10 micrograms/ml) also appeared to be associated with both systems. The presence of the Gm1,17;..;21 haplotype was associated with decreased lymphocyte reactivity, whereas the B8/DR3 phenotype was associated with high responsiveness to these mitogens. However, in the presence of the Gm1,17;..;21 haplotype subjects positive for HLA-B8/DR3 did not respond better to mitogenic stimulation than those lacking this HLA haplotype. Our results imply that the immunogenetic make-up of test persons should be taken into account in the assessment of the immune status of individuals or groups of patients.

Adult↗

Development of connective tissue disease in patients presenting with Raynaud's phenomenon: a six year follow up with emphasis on the predictive value of antinuclear antibodies as detected by immunoblotting.

Eighty five patients referred because of Raynaud's phenomenon (RP) were followed up for six years. Every two years they were screened for signs and symptoms of connective tissue disease (CTD) according to a protocol, and serum was stored. Initially, 30 patients had primary RP, 16 had one symptom of CTD ('possible CTD'), 18 had two or more symptoms ('probable CTD'), and 21 had definite CTD (14 of whom had scleroderma). Most of the symptoms were related to scleroderma. There was an insidious progression to scleroderma or CRST syndrome (calcinosis, Raynaud's phenomenon, sclerodactyly, telangiectasia): 11 of 46 patients with primary RP or possible CTD developed probable scleroderma (two or more symptoms but not fulfilling all criteria), and seven of 13 patients with probable scleroderma developed definite scleroderma or CRST. The presence of distinct antinuclear antibodies (ANAs) as detected by immunoblotting in patients with primary RP and possible CTD at the start of the study was associated with the evolution of symptoms of CTD (chi 2 = 5.7, p less than 0.01). In patients initially with primary RP or possible CTD the antibody specificities of ANAs as determined by immunoblotting had prognostic value for the development of certain disease entities: anticentromere (CR-19) for CRST (sensitivity 60%, specificity 98%) and antitopoisomerase I (Scl-70 or Scl-86) for scleroderma or probable scleroderma (sensitivity 38%, specificity 100%).

Adult↗