Journal of Clinical Pathology, 1979, 32, 897-901
Serum immunoreactive trypsin concentrations in infectious and non-infectious illnesses and in juvenile diabetes D. R. GAMBLE', ANNE MOFFATT2, AND VINCENT MARKS2 From the 'Public Health Laboratory, West Park Hospital, Epsom, Surrey KTJ9 8PB, and the 2Department of Clinical Biochemistry, St Luke's Hospital, Warren Road, Guildford, Surrey GU] 3NT, UK.
Serum immunoreactive trypsin (SIT) concentrations were measured in 244 patients with infectious illnesses and in 281 children with diabetes of recent onset. Results were compared with reference ranges established in 107 patients with non-infectious, non-diabetic illnesses, in whom SIT concentrations were found to increase with advancing age. Reduced or undetectable concentrations of SIT were associated with diabetes in children and with a few cases of severe childhood infection. Increased SIT concentrations were associated with virologically confirmed cases of infection with mumps and Coxsackie B virus infection, and with clinical diagnoses of mumps, PUO, and meningitis in children, and with Bornholm disease, cardiac infection, and respiratory infection in adults. It is suggested that silent invasion of the exocrine pancreas with elevation of the SIT concentration may accompany infection by Coxsackie B, mumps, and, possibly, other viruses.
SUMMARY
Trypsin, or more properly its inactive precursor of subjects: patients with non-infectious illnesses, trypsinogen, is, in contrast to other pancreatic patients with a variety of infections, and patients enzymes, produced solely by the pancreas. It has with juvenile diabetes. therefore been suggested that a recently developed radioimmunoassay for measuring its concentration Patients and methods in serum might provide a specific test of pancreatic exocrine functions (Elias et al., 1977). However, All specimens tested were surplus from samples non-pancreatic factors such as hormones, anti- submitted for microbiological investigation. Almost bodies, and the rate or extent of its reabsorption all were sent through the post at ambient temperafrom the gut may also affect serum immunoreactive trypsin (SIT) concentrations, and a full understanding of these interactions will require new experimental data. Published studies suggest that the SIT concentration may be high in cases of acute pancreatitis or chronic renal failure (Temler and Felber, 1976; Elias et al., 1977) and high, normal, or low in cases of chronic pancreatitis and pancreatic carcinoma, depending perhaps on the stage of the disease (Bambule-Dick et al., 1978; Adrian et al., 1979; Minaire et al., 1979). In diabetes, low levels have been reported in patients treated with insulin or sulphonylureas but not in those treated with biguanides (Dandona et al., 1978). In the present study we have assayed SIT concentrations in three groups Received for publication 13 February 1979
ture as unfrozen whole blood or serum, and bacterial contamination was sometimes present. Sera were stored at - 20'C on receipt but were thawed and refrozen a number of times for a variety of other
tests.
Preliminary results showed that SIT levels were often raised in patients with certain infectious illnesses and depressed in diabetics. Specimens from normal children were not obtainable, so a 'control' group was assembled from 107 patients comprising 55 children aged 0-14 years and 52 adults with illnesses unlikely to be due to infection, diabetes, or other pancreatic disease. The diagnoses in these 'control' patients were: psychiatric illness (46) and ophthalmological (14), arthritic (13), neurological (7), gastrointestinal (7), and other (20) diseases. Altogether 244 patients with putative infectious illnesses were tested. These comprised 132 children 897
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D. R. Gamble, Anne Moffatt, and Vincent Marks
and 112 adults, selected to include a range of clinical diagnoses (Table 1), but particularly those associated with infectious agents known to cause pancreatitis (mumps virus, Coxsackie B virus, and Mycoplasma pneumoniae). In 63 of these patients a specific infectious agent was implicated by microbiological tests (Table 2). The diabetes group comprised 281 children notified to the British Diabetic Association Register of Newly Diagnosed Diabetic Children (Bloom et al., 1975). The duration of diabetic symptoms at
the time of blood collection was up to eight years, but was less than one year in 260 (92%). SIT concentrations were measured by radioimmunoassay using a double antibody technique (Elias et al., 1977). Highly purified human trypsin was used as immunogen and for radioiodination. Antibodies were produced in rabbits. Radioiodination was performed by the chloramine-T method using l251-labelled sodium iodide. Standards used in the assay were made from a semipurified preparation of human trypsin, and they ranged from
Table 1 Serum immunoreactive trypsin levels by clinical diagnosis Number tested
Diagnosis
Patients outside 'reference' ranges (see text) Serum trypsin
Lymphadenopathy Pyrexia of uncertain origin
Lower respiratory infection
31 24
21
760 460 400 390 360 70 790 470 0 0
Upper respiratory infection
31
510 70 60 60 50
20
23
Meningitis
Bornholm disease
Myocarditis
or
pericarditis
Other infections: Rash Mumps Mumps Septic arthritis Convulsions Rash Encephalitis
Infections-total Insulin dependent diabetes Non-infectious illness in nondiabetic patients
13
33
Above normal
6
0/31 5/24
NS