Elevated IgG4 levels in patients demonstrating sarcoidosis-like radiologic findings

One of the radiologic patterns associated with IgG4-related systemic disease was similar to that of pulmonary sarcoidosis. We analyzed whether suspected pulmonary sarcoidosis might include unrecognized IgG4-related systemic disease. The enrolled patients had bilateral hilar lymphadenopathy and/or lung nodules on chest computed tomography, used to diagnose the patients who could either be compatible with or suggested as having pulmonary sarcoidosis. The IgG4 levels were retrospectively measured. Bronchoalveolar lavage (BAL) was analyzed for the presence of IgG subclasses, and specimens were stained by an antibody to IgG4. We compared these data in the suspected sarcoidosis patients, with or without elevated serum IgG4, with the laboratory data and bronchoscopy results in patients with definite sarcoidosis. All enrolled patients were followed for over 5 years. The patients were classified as 49 definite and 44 suspected sarcoidosis patients. Eight patients, including 6 suspected sarcoidosis patients, had elevated abnormal levels of serum IgG4. The suspected sarcoidosis patients had significantly lower percentages of lymphocytes and IgG in the BAL. One suspected sarcoidosis patient had positive IgG4 staining in a lung specimen. The elevated serum IgG4 patients among the patients with suspected sarcoidosis showed significantly higher levels of BAL IgG4, IgG4/IgG, and IgG4/IgG3 compared with the levels of the normal serum IgG4 patients. The follow-up study revealed that 1 patient with elevated serum IgG4 was complicated with other organ failure caused by IgG4-related systemic disease, and Castleman disease was diagnosed in 2 patients. IgG4-related systemic disease was, therefore, identified among the patients with elevated serum IgG4.     

Altered gastrointestinal immune response in sarcoidosis.

Because of the possible clinical association between coeliac disease and sarcoidosis, the incidence of humoral sensitivity to dietary proteins was examined in patients with sarcoidosis. Raised concentrations of circulating IgG antibodies to alpha gliadin were found in 41/99 sarcoid patients whereas antibody levels to casein, beta lactoglobulin and ovalbumin were similar to normal controls. Subsequently, a group of 26 sarcoid patients were selected for small intestinal biopsy; 11 had raised and 15 normal alpha gliadin antibody (AGA) levels. One AGA positive patient had villous atrophy consistent with coeliac disease. Intraepithelial lymphocyte (IEL) counts were raised in AGA positive (median 30; 95% confidence limits 22-46) and AGA negative (median 24; 95% confidence limits 19-32) sarcoid patients when compared with a control group (median 13.5; 95% confidence limits 10-18) p less than 0.01. Serum IgG concentrations were raised in 11/52 patients tested but there was no correlation between IgG levels and the presence of IgG antigliadin antibodies. HLA Dr typing was done in 21 of the 26 biopsied patients. The coeliac disease associated antigen Dr3 was present in eight of 21 (38%) which is very similar to the prevalence in unselected blood donors (34%). There was no significant difference in IEL counts between Dr3 positive and Dr3 negative sarcoid patients. These findings suggest that in patients with sarcoidosis, there is an altered gastrointestinal mucosal immune response, accompanied in about 40% of patients by specific sensitisation to wheat protein.     

Diagnosis and parameters for the evaluation of disease activity and prognosis in patients with pulmonary sarcoidosis

We evaluated the usefulness of serum ACE, BALF lymphocyte%, CD4+/CD8+ ratio when diagnosing pulmonary parenchymal lesion in patients with sarcoidosis. The results showed the substantial usefulness but lesser specificity. Furthermore, we evaluated the values of the above three parameters in terms of the judgment of the disease activity and the reliability for foreseeing the prognosis in BHL sarcoidosis. Elevated serum ACH had a good relationship with the disease activity in both nonsmoker and smoker cases. BALF lymphocyte % also had in smoker cases. But none of three parameters showed a significant relationship with the prognosis in BHL sarcoidosis.     

Clinical study on soluble interleukin-2 receptor in patients with sarcoidosis]

Levels of soluble IL-2 receptor in sera of 18 patients with sarcoidosis were measured by a sandwich ELISA method established by the authors and were found to be significantly higher than those in sera of normal subjects. Levels of soluble IL-2 receptor in sera of sarcoidosis cases of bilateral hilar lymphadenopathy (BHL) were significantly higher than those in sera of sarcoidosis cases without BHL. In patients with sarcoidosis, levels of soluble IL-2 receptor did not differ in relation to the presence or absence of ocular lesions, or in relation to positive or negative response to protein purified derivative of tuberculosis (PPD).     

A case of elderly onset sarcoidosis

Although sarcoidosis is generally considered a disease of young and middle aged adults, there have been a certain number of cases among elderly. However it is unknown whether sarcoidosis in the elderly is recurrence of prior disease or initial onset at old ages. We present a 77-year-old woman with sarcoidosis the onset of which was considered to be in the last 6 months prior to the initial diagnosis. The patient was admitted to our hospital for further evaluation of bilateral hilar and mediastinal lymphadenopathy (BHL) and uveitis. BHL was not present in a chest radiograph taken 6 months prior to the admission. A clinical diagnosis of sarcoidosis was made by elevated serum angiotensin converting enzyme (ACE) and lysozyme (24.9 IU/L and 18.2 micrograms/ml, respectively), negative tuberculin skin test, concomitant presence of uveitis, and a high proportion of lymphocytes (33.2%) in bronchoalveolar lavage fluid with an elevated CD4/CD8 ratio (24.5). This is a noteworthy case of sarcoidosis in which we could confirm elderly onset of the disease.     

Nitric oxide levels in exhaled air and inducible nitric oxide synthase immunolocalization in pulmonary sarcoidosis.

Cytokines such as tumour necrosis factor-alpha and interferon gamma are associated with active pulmonary inflammation in sarcoidosis and they upregulate inducible nitric oxide synthase (iNOS). The objectives of this study were to examine iNOS upregulation in sarcoidosis by showing raised exhaled nitric oxide and increased iNOS activity in lung biopsy specimens of these patients utilizing immunohistochemistry. Exhaled NO was measured by a chemiluminescence analyser in 12 patients with newly diagnosed biopsy-proven sarcoidosis before and after 6 weeks of corticosteroid therapy. Lung biopsy specimens from these patients were subjected to immunohistochemical staining with a specific iNOS antibody. Exhaled NO was raised in newly diagnosed sarcoidosis (mean+/-SEM): 9.8+/-0.4 versus 4.1+/-0.2 parts per billion (ppb) in 21 healthy controls, p<0.001; and fell significantly after 6 weeks treatment with corticosteroids to 5.9+/-1.4 ppb; p<0.01. There was no correlation between exhaled NO and other markers of disease activity. Immunohistochemical staining demonstrated iNOS activity in respiratory epithelium and granulomas in patients with sarcoidosis. Exhaled nitric oxide is raised in patients with active pulmonary sarcoidosis and may be a result of inducible nitric oxide synthase upregulation. The fall in exhaled nitric oxide following corticosteroid therapy may reflect inhibition of inducible nitric oxide synthase in the respiratory epithelium and granulomas.     

Significance of lymphocytosis in bronchoalveolar lavage in suspected ocular sarcoidosis.

Ocular sarcoidosis is frequent in Japan, but in many cases the condition remains undiagnosed in patients with suspected ocular sarcoidosis. Bronchoalveolar lavage (BAL) was performed in order to study the clinical implications of lymphocytosis of BAL fluid in such patients with characteristic ocular manifestations. The subjects included in this study were 39 patients with suspected ocular sarcoidosis. The patients were divided into four types based on high-resolution computed tomography (HRCT) findings; no lung involvement (HRCT-0), bilateral hilar lymphadenopathy (BHL) without lung involvement (HRCT-I), lung involvement and BHL (HRCT-II), and lung involvement and no BHL (HRCT-III). Transbronchial lung biopsy (TBLB) and BAL were conducted after examining serum angiotensin-converting enzyme and serum lysozyme values, skin test for purified protein derivative chest radiograph, HRCT, and gallium scintigram. Twenty patients were histologically diagnosed as having sarcoidosis, and 19 patients remained undiagnosed. Granuloma was identified by TBLB in 19 of 20 patients in type HRCT-II but in only one of 19 patients in types HRCT-0 and HRCT-I (p<0.0001). Lymphocytosis in BAL (>15%) was identified in all patients who showed lung field involvement (type HRCT-II) and in 16 of 19 patients without lung field involvement (types HRCT-0 and HRCT-I). There were 10 patients whose only relevant findings were lymphocytosis in BAL. Among these 10 patients, an increased CD4+/CD8+ ratio (>3.5) in BAL was seen in 60%. The authors conclude that high-resolution computed tomography results yield the same degree of diagnostic accuracy as transbronchial lung biopsy in ocular sarcoidosis suspects. However, bronchoalveolar lavage revealed significant lymphocytosis in patients with negative high-resolution computed tomography results. It should be kept in mind that a diagnostic group of patients with sarcoidosis who manifest ocular involvement and lymphocytosis in bronchoalveolar lavage exists.     

Presence of antinucleosome autoantibodies in a restricted set of connective tissue diseases: antinucleosome antibodies of the IgG3 subclass are markers of renal pathogenicity in systemic lupus erythematosus

OBJECTIVE: To study the frequency and disease specificity of antinucleosome antibody reactivity in diverse connective tissue diseases (CTD), and to determine factors, such as antibody subclass, that may influence the pathogenicity of these antibodies in relation to disease activity. METHODS: IgG and IgM antinucleosome activities on nucleosome core particles from 496 patients with 13 different CTD and 100 patients with hepatitis C were measured by enzyme-linked immunosorbent assay (ELISA). Of the patients with CTD, 120 had systemic lupus erythematosus (SLE), 37 had scleroderma (systemic sclerosis; SSc), 20 had mixed connective tissue disease (MCTD), and 319 had other CTD, including Sj?gren's syndrome, inflammatory myopathy, rheumatoid arthritis, primary antiphospholipid syndrome, Wegener's granulomatosis, Takayasu arteritis, giant cell arteritis, relapsing polychondritis, Beh?et's syndrome, and sarcoidosis. Antinucleosome-positive sera were further analyzed, by isotype-specific ELISA, for antinucleosome and anti-double-stranded DNA (anti-dsDNA) IgG subclasses. RESULTS: SLE, SSc, and MCTD were the only 3 CTD in which antinucleosome IgG were detected (71.7%, 45.9%, and 45.0% of patients, respectively). Antinucleosomes of the IgG3 subclass were present at high levels in patients with active SLE and were virtually absent in those with SSc, MCTD, or inactive SLE, and their levels showed a positive correlation with SLE disease activity. Of note, an increase in levels of antinucleosome of the IgG3 isotype was observed during SLE flares, and this increase was found to be closely associated with active nephritis. Levels of antinucleosome of the IgG1 subclass showed a trend toward an inverse correlation with SLE disease activity. No significant fluctuation in the anti-dsDNA isotype profile was observed in relation to SLE severity or clinical signs. CONCLUSION: Our data suggest that IgG antinucleosome is a new marker that may help in the differential diagnosis of CTD; antinucleosome of the IgG3 isotype might constitute a selective biologic marker of active SLE, in particular, of lupus nephritis.     

Sarcoidosis with acute recurrent polyarthritis and hypercalcemia

A 45-year-old woman had bleary eyes and recurrent episodes of fever and arthritis in the knees and ankles. The patient had anterior uveitis, negative findings of the tuberculin test, and an increased serum lysozyme level, but bilateral hilar lymphadenopathy (BHL) was absent. During the course of her disease, the serum calcium and angiotensin-converting enzyme levels gradually increased to above the normal level, and the patient was clinically diagnosed as having sarcoidosis. The clinical features of arthritis were typical of those of L?fgrens syndrome although BHL and erythema nodosum were absent. The patient was successfully treated with 15 mg/day of prednisolone.     

Elevation of serum angiotensin-converting-enzyme (ACE) level in sarcoidosis.

The level of serum angiotensin-converting enzyme (ACE) was elevated in 15 of 17 patients with active sarcoidosis. Serum ACE was studied to determine the effect of chronic lung disease upon the blood level of an enzyme believed to originate from the lungs. The assay was performed in approximately 200 control subjects and 200 patients with chronic lung disease using hippuryl-L-histidyl-L-leucine as substrate. Enzyme activity greater in male control subjects than in female subjects of comparable age and greater in children than in adults. Serum ACE was significantly reduced in patients with chronic obstructive lung disease, lung cancer, tuberculosis and cystic fibrosis, as compared to control subjects, and was even lower in those receiving corticosteroids. Of greatest interest, however, was that levels in patients with active sarcoidosis not receiving steroids were greater than 2 standard deviations above the mean for the adult control subjects (greater than 11.6 units) whereas levels in patients with sarcoidosis receiving steroids and in those with resolved disease were normal. A survey of subjects with other granulomatous diseases failed to reveal any other condition that was significantly associated with a similar elevation of serum ACE levels. Elevation of ACE levels in sarcoidosis appears to be associated with the active disease process and does not appear to be a familial inherited enzyme abnormality. An assay of serum ACE is a useful tool for regulating therapy in sarcoidosis and for confirming the diagnosis, since it readily distinguishes these patients from others with tuberculosis, lung cancer or lymphoma.     

Bronchoalveolar lavage fluid D dimer levels are higher and more prevalent in black patients with pulmonary sarcoidosis

BACKGROUND: Abnormalities of lung coagulation and fibrinolysis in sarcoidosis are thought to play a role in the pathogenesis of this disease. OBJECTIVE: We previously showed that bronchoalveolar lavage fluid (BALF) D dimer directly correlated with various measures of severity in sarcoidosis. Here, we analyze our observation that BALF D dimer was more frequently found at higher levels in African-American patients with pulmonary sarcoidosis. METHODS: BALF D dimer was measured in 55 subjects with pulmonary sarcoidosis and 31 healthy volunteers by enzyme immunoassay. The healthy group established a normal range of BALF D dimer with 71 ng/ml as the highest measured level. This was the cut point for comparisons among the patients with sarcoidosis. RESULTS: High BALF D dimer levels (>71 ng/ml) were found in younger patients with sarcoidosis and were associated with a significantly lower percent predicted forced expiratory volume in 1 s and greater numbers of BAL lymphocytes. Black patients with sarcoidosis had higher BALF D dimer levels (median 131, range 0-2,040 ng/ml) than white patients (median 18, range 0-605 ng/ml; p = 0.011). Higher than normal BALF D dimer levels were found in 61% of the black subjects with sarcoidosis, but in only 20% of the white individuals (chi(2) = 5.539, p = 0.019). BALF D dimer was the only disease measure that discriminated black from white individuals with sarcoidosis. CONCLUSION: BALF D dimer is an indicator of lung fibrin formation and degradation in sarcoidosis. The relationship of high D dimer levels with greater BAL lymphocytosis and worse lung function may be a marker of active sarcoidosis, especially in African-Americans who tend to suffer a more serious form of the disease.     

Metastatic renal cell carcinoma simulating sarcoidosis. Analysis of 12 patients with bilateral hilar lymphadenopathy

Case summaries of four patients with bilateral hilar lymphadenopathy (BHL) caused by metastatic renal cell carcinoma are presented, and these and eight similar cases from the literature are analyzed. In nine patients, sarcoidosis was the provisional clinical diagnosis, but four of these patients had a past history of renal cell carcinoma. In the remaining five patients, a distinction from sarcoidosis could not be made by history, physical examination, and chest roentgenogram. This underscores the need for tissue confirmation in the diagnosis of sarcoidosis and alerts the physician to consider metastatic renal cell carcinoma in the differential diagnosis of BHL.     

A comparison of albumin and urea as reference markers in bronchoalveolar lavage fluid from patients with interstitial lung disease

Lavage fluids were investigated for 67 subjects in 6 groups: 12 with active sarcoidosis, 8 with inactive sarcoidosis, 17 with pigeon breeder's disease, 10 asymptomatic pigeon breeders, 12 with idiopathic pulmonary fibrosis (IPF) and 8 normal subjects. Albumin and urea per ml of bronchoalveolar lavage fluid (BALF) were determined for each subject together with percentage return of fluid (BAL%). Novel assay systems were employed to measure urea and albumin and these were compared with existing analytical techniques. When compared with the control group, we found that urea per ml of BALF was not statistically different for all other groups, except those with pigeon breeder's disease who had significantly raised levels. For albumin, however, three groups had significantly higher levels than the controls, namely those with active sarcoidosis, pigeon breeder's disease and IPF. BAL% return showed no significant differences for any group when compared with the controls. We conclude that since albumin is significantly raised in most patients with interstitial lung disease it does not represent a suitable marker for the quantitation of reactive proteins in BALF. Urea shows much less variability between groups than does albumin, and hence in the absence of a proven alternative represents the most reliable estimate available of epithelial lining fluid dilution during the lavage procedure, providing dwell time is kept to a minimum.     

Acute-onset sarcoidosis with erythema nodosum and polyarthralgia (Löfgren's syndrome) in Japan: a case report and a review of the literature

L?fgren's syndrome is an acute form of sarcoidosis that is characterized by erythema nodosum (EN), bilateral hilar lymphadenopathy (BHL), and polyarthralgia or polyarthritis. This syndrome is common among white people, but is considered rare among Japanese people. We present the case of a 26-year-old Japanese woman with L?fgren's syndrome. The patient complained of polyarthritis and EN of the lower extremities that lasted for 3 months. A chest radiograph revealed BHL and nodular shadows. The angiotensin-converting enzyme (ACE) level was within the normal range. Transbronchial lung biopsy revealed a noncaseating granuloma with giant cells. Six Japanese cases of L?fgren's syndrome have been reported previously. Five of the seven Japanese patients with L?fgren's syndrome had normal ACE levels; all of them exhibited BHL. L?fgren's syndrome should be considered as a possibility when examining a patient with EN and articular symptoms, even if the patient is Japanese.     

Systemic phenotype of sarcoidosis associated with radiological stages. Analysis of 1230 patients

BackgroundTo analyze the association between Scadding radiological stages of sarcoidosis at diagnosis and the disease phenotype (epidemiology, clinical presentation and extrathoracic involvement) in one of the largest cohorts of patients with sarcoidosis reported from southern Europe.MethodsThe SARCOGEAS-Study Group includes a multicenter database of consecutive patients diagnosed with sarcoidosis according to the WASOG 1999 criteria. Extrathoracic disease at diagnosis was defined according to the 2014 instrument and the clusters proposed by Schupp et al.ResultsWe analyzed 1230 patients (712 female, mean age 47 yrs.) who showed the following Scadding radiologic stages at diagnosis: stage 0 (n = 98), stage I (n = 395), stage II (n = 500), stage III (n = 195) and stage IV (n = 42). Women were overrepresented in patients presenting with extrathoracic/extrapulmonary disease, while the diagnosis was made at younger ages in patients presenting with BHL, and at older ages in those presenting with pulmonary fibrosis (q values <0.05). Multivariable adjusted analysis showed that patients presenting with pulmonary involvement (especially those with stages II and III) had a lower frequency of concomitant systemic involvement in some specific extrathoracic clusters (cutaneous-adenopathic/musculoskeletal, ENT and neuro-ocular/OCCC) but a higher frequency for others (hepatosplenic), in comparison with patients with extrapulmonary involvement (stages 0 and I). The presence of either BHL or fibrotic lesions did not influence the systemic phenotype of patients with pulmonary involvement.ConclusionsThe key determinant associated with a differentiated systemic phenotype of sarcoidosis at diagnosis was interstitial pulmonary involvement rather than the individual Scadding radiological stage.     

Computed tomographic scanning in sarcoidosis

Sarcoidosis is a granulomatous disease of unknown etiology that involves the lungs or intrathoracic lymph nodes in more than 90% of patients. The clinical spectrum of sarcoidosis is protean, but pulmonary manifestations often dominate. Chest radiographs are abnormal in 90 to 95% of patients with sarcoidosis; the most characteristic feature is bilateral hilar lymphadenopathy (BHL), present in 50 to 80% of patients. Pulmonary parenchymal infiltrates are present in 25 to 50% of patients. In this article, we review the radiographic features of sarcoidosis (both typical and atypical), and the impact of chest radiographic stage on long-term prognosis. Computed tomographic (CT) scans are more sensitive than chest radiographs in delineating parenchymal, mediastinal, and hilar structures, and distinctive CT patterns may be virtually pathognomonic for sarcoidosis in some patients. Routine CT scan is not appropriate to diagnose or manage sarcoidosis, but CT may be invaluable in patients with atypical clinical or chest radiographic findings or specific complications of sarcoidosis (pulmonary or extrapulmonary), or to assess prognosis. High-resolution thin-section CT scans (HRCT) may be helpful in selected patients with stage II or III sarcoidosis to discriminate active inflammation from irreversible fibrosis. This article discusses the salient HRCT features of sarcoidosis, accuracy of CT in the differential diagnosis, and correlations of HRCT with disease extent and activity, pulmonary function, and lesion reversibility.     

Increased levels of nerve growth factor in the airways of patients with sarcoidosis

Objectives. Nerve growth factor (NGF) is a potent neuronal growth factor with inflammatory properties that recently has been proposed to be of importance in airway pathology. A role for NGF in the inflammatory granulomatous lung disease sarcoidosis is not well elucidated. The aims of this study were to investigate the secreted levels of NGF in bronchoalveolar lavage fluid (BALF) from sarcoidosis patients compared with patients with resolved disease, patients with another granulomatous disease – chronic beryllium disease (CBD) – and healthy subjects and also to investigate the relationship between NGF levels and markers of inflammation. Methods and results. NGF levels in BALF from 56 patients with active sarcoidosis (22 with Löfgren’s syndrome), nine subjects with resolved sarcoidosis, six patients with CBD, and 31 healthy subjects were compared. A 10‐fold elevation of NGF levels was found in patients with active sarcoidosis compared with subjects with clinically resolved sarcoidosis, patients with CBD and healthy subjects. In sarcoidosis patients, positive correlations between concentrations of NGF and lymphocytes, eosinophils and interferon‐γ, interleukin (IL)‐4, IL‐10, IL‐12 were found. Conclusions. We demonstrate that secreted levels of NGF are markedly enhanced in the airways in active pulmonary sarcoidosis. Furthermore, a relationship between NGF and pulmonary inflammation in sarcoidosis is supported.     

Elevated serum neopterin levels in sarcoidosis

Neopterin levels have been reported elevated in diseases with changed cellular immune response. The study reported here was designed to examine whether serum neopterin (S-neopterin) could be a marker of activity in sarcoidosis. S-neopterin was measured by radioimmunoassay in 37 patients with inactive and 34 patients with active sarcoidosis and in 38 controls. The levels were significantly elevated in both sarcoid groups and increased in stage III compared to I and II. S-neopterin levels were significantly correlated to levels of serum angiotensin-converting enzyme (SACE) and immunoglobulins IgG and IgA. The results indicate that S-neopterin may be a marker of activity in sarcoidosis.     

Elevated level of soluble HLA class I antigens in serum and bronchoalveolar lavage fluid in patients with sarcoidosis

OBJECTIVE: Soluble HLA class I antigens (sHLAs) in human serum have been reported to be associated with allografts and autoimmune disease and could modify immunological reactions induced by membrane type HLAs. To investigate the clinical significance of sHLAs in sarcoidosis, we assessed concentrations of sHLAs in both serum and bronchoalveolar lavage fluid (BALF) and also examined their production by peripheral blood mononuclear cells (PBMCs) and BALF cells. METHODS: Concentrations of sHLAs were determined by enzyme-linked immunosorbent assay, using a monoclonal antibody against HLA class I (W6/32) and an enzyme-labeled polyclonal antibody to human beta2-microglobulin. PBMCs and BALF cells were cultured in the presence or absence of either LPS or PHA. PATIENTS: Serum levels of sHLAs were assessed in 96 patients with sarcoidosis and in 32 healthy control subjects. sHLAs concentrations in BALF were also investigated in 17 active sarcoidosis patients and in 13 control subjects. RESULTS: sHLAs levels in both serum and BALF were higher in sarcoidosis cases than in control subjects (p<0.05, in both). In the patients, values were significantly higher in active than in inactive stages (p<0.001) and significantly correlated with angiotensin-converting enzyme (ACE) levels. Both PBMCs and BALF cells produced enhanced amounts of sHLAs in patients with active sarcoidosis compared with those in control subjects. CONCLUSION: These results demonstrated that the level of sHLAs in serum is a useful index of disease activity of sarcoidosis, partly reflecting production by PBMCs and BALF cells.     

Agalactosyl IgG in inflammatory bowel disease: correlation with C-reactive protein.

The proportion of oligosaccharide chains on the Fc fragment of IgG which terminate with N-acetylglucosamine (GlcNAc) rather than galactose is increased in rheumatoid arthritis and tuberculosis, and in sera from patients with Crohn's disease, probably because of decreased activity of a galactosyltransferase in B lymphocytes. We have assayed the prevalence of agalactosyl oligosaccharides on IgG in sera from 67 patients with inflammatory bowel disease (32 ulcerative colitis and 35 Crohn's disease). The prevalence of agalactosyl IgG significantly increases in the majority of Crohn's patients (19/35 patients), and correlates with the level of C-reactive protein (r = 0.79), and inversely with the concentration of serum albumin. Sera from ulcerative colitis patients show less frequent (nine of 32) and less marked rises in agalactosyl IgG, and sera with high C-reactive protein values can contain normal levels. Thus in ulcerative colitis no correlation was seen between the two assays. The diseases in which the percentage of agalactosyl IgG is raised (rheumatoid arthritis, tuberculosis, Crohn's disease and some ulcerative colitis) are characterised by simultaneous T cell mediated granulomatous tissue damage, and acute phase responses. Levels are normal in less tissue damaging granulomatous conditions, including sarcoidosis, and leprosy (except during episodes of erythema nodosum leprosum). We suggest therefore that a raised percentage of agalactosyl IgG is a correlate of a particular type of T cell mediated pathology which may be relevant to the pathogenesis of inflammatory bowel disease.