Abstract
All serum protein electrophoresis (SPE) results obtained between 2002 and 2009 from clinical cases presented to the University of Bristol Feline Centre were examined retrospectively. One hundred and fifty-five results met the inclusion criteria. Signalment and final diagnoses were obtained from the case records. Clinical cases were classified as having normal or abnormal SPE results by comparison to reference intervals for SPE created using 77 clinically normal cats. Abnormal results were then further divided according to the specific SPE abnormality. Cases were also categorised, according to the final diagnosis, using the DAMNITV classification system. Of the 155 cases, 136 (87.7%) had abnormal SPE results, most commonly due to a polyclonal increase in gamma globulins. A monoclonal gammopathy occurred in four cats; one with feline infectious peritonitis (FIP), one with lymphoma and two cases of splenic plasmacytoma (one suspected, one confirmed). The most common DAMNITV classification associated with SPE abnormalities was infectious/inflammatory disease (80/136; 58.8%), including 39 cats diagnosed with FIP.
Serum protein electrophoresis (SPE) is a laboratory test used to separate serum proteins based on their size and electrical charge. The proteins are separated on agarose gel following application of an electrical charge, then stained, and their density is analysed using a densitometer. A graphical trace is produced called an electrophoretogram with the proteins separated into four fractions; albumin, and alpha (α), beta (β) and gamma (γ) globulins; α and β globulins are further divided into α-1 and −2 and β−1 and −2 (Fig 1). The percentage contribution of each fraction multiplied by the total protein concentration provides approximate protein concentrations for each fraction. 1–3
Fig 1.
An example of an SPE densitometer trace (bottom) and agarose strip (top), illustrating the separation of proteins into different categories and subsequent quantification.
The α globulins include some acute phase proteins (APPs) (ceruloplasmin, haptoglobin, α-2-macroglobulin) and are elevated in the presence of acute inflammation but also with malignancy and nephrotic syndrome. β globulins include transferrin, a negative APP, and lipoproteins, complement and immunoglobulins, mainly IgA or IgM. Increases in the β fraction occur with inflammation, neoplasia and various metabolic conditions. 4 Elevations in the γ fractions tend to be associated with chronic antigenic stimulation, as this fraction is composed of immunoglobulins, particularly IgG, but also the APP C-reactive protein. 4 Elevations in this region are described as either polyclonal, when the increase in immunoglobulins is produced by a heterogenous population of B-cells, or monoclonal with a single protein producing a narrow peak on the electrophoretic trace. Monoclonal spikes are associated with lymphoproliferative diseases such as malignant plasma cell disorders (multiple myeloma and extramedullary plasmacytoma) and lymphoma, but are also reported with infectious disease, immune-mediated disease and Waldenström's macroglobulinaemia in humans 5 and dogs. 6,7
Feline SPE results have been described infrequently other than in association with feline infectious peritonitis (FIP). 8–10 The electrophoretic pattern seen in experimental FIP infection includes early increases in α-2 globulins followed by a smooth polyclonal increase in γ globulins. 8 Cases of naturally occurring FIP, when the duration of infection is unknown, have shown more variable combinations of the above abnormalities. 9,10 The electrophoretic patterns of cats infected with feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) have recently been reported; with FIV positive cats showing polyclonal hypergammaglobulinaemias. 11 FeLV positive cats showed more varied γ globulin levels and significantly higher α-2 globulins. 11 Monoclonal gammopathies associated with plasma cell neoplasias, 12,13 and infrequently associated with ehrlichia, anaplasma and FIP infection 14–18 have been described.
To the authors’ knowledge, no previous study has evaluated the SPE results of a large number of clinical feline cases. The aims of this study were to create a laboratory reference interval for feline SPE and to use this to evaluate retrospective SPE results obtained in cats over a 7-year period at a veterinary referral centre. SPE results were classified as normal or abnormal and the associated diseases were described.
Materials and Methods
SPE methodology
Electrophoresis was performed on agarose gels using the Beckman Paragon system (Beckman-Coulter, High Wycombe, UK), according to the manufacturer's instructions using 50 μl serum. Gels were analysed on a GS-700 imaging densitometer using the manufacturer's Molecular Analyst software (Bio-rad, Hemel Hempstead, UK). The concentration of individual fractions was determined by multiplying the percentage volume of the fraction by the sample total protein concentration measured using the biuret method (Konelab, Inverness Medical, Stockport, UK). All analyses were performed and read by a single operator (SJD).
Calculation of SPE reference intervals
Reference intervals for SPE values for the laboratory were created by SPE analysis of excess serum samples available from healthy cats, obtained as part of the Pet Travel Scheme (‘normal group’). Cats were examined at the time of sampling and reported by the attending veterinarian to be clinically healthy. The reference intervals were created using 95% of the healthy population.19
Retrospective analysis of SPE results from clinical cases
SPE results from clinical cases presented to the University of Bristol Feline Centre between January 2002 and April 2009 inclusive were examined (‘clinical group’). Inclusion criteria included the availability of SPE results and complete clinical records. Signalment and final diagnosis from each case were retrieved from the clinical records. Cases within the clinical group were classified as having normal or abnormal SPE results, based on the calculated reference intervals, and were further grouped according to the abnormal protein fraction identified. Those with elevated γ globulins were described as having monoclonal or polyclonal elevations, with a monoclonal gammopathy defined as a narrow peak in the γ globulin region with a base similar in width to the albumin band or a peak height at least four times the peak width. 2,6
The cases were also divided according to the DAMNITV classification (degenerative, anomalous, metabolic, neoplastic, inflammatory/infectious, traumatic/toxic, vascular), as previously reported. 20,21 Cases with more than one diagnosis within the same DAMNITV group were noted. Cases with more than one diagnosis in different DAMNITV groups featured in all relevant DAMNITV groups but contributed only once to the total number of cases with that specific SPE abnormality. If no diagnosis (ND) was reached, this was also recorded. Cases of FIP were classified as ‘confirmed’ if histopathology confirmed a diagnosis of FIP, or ‘suspected’ if the attending referral clinician concluded that FIP was the most likely diagnosis based on clinical signs, laboratory results and outcome, but for which histopathology was not available. Additionally, within the clinical group, those cats diagnosed with FIP (suspected or confirmed) were selected and their SPE results described further.
Statistical analysis
Data were tested for normality using the D’Agostino and Pearson omnibus normality tests where indicated. For normal distributions means and standard deviations were calculated, and for non-normally distributed data medians and ranges were calculated.
The χ2 test, two-tailed Student's t-test or Mann–Whitney U test were used to assess differences in signalment between the normal group and the clinical group depending on whether categorical, normally distributed data or non-normally distributed data were being analysed, respectively.
Statistical analysis was performed using a statistical package (Graphpad Prism version 5 for Windows, Graphpad Software, San Diego, USA). Significance was taken as P<0.05.
Results
Calculation of SPE reference intervals
Seventy-seven serum samples from clinically normal cats underwent SPE. These SPE data were not normally distributed. The calculated reference intervals are shown in Table 1
Table 1.
Reference intervals for feline SPE.
| Region | Albumin | α-1 | α-2 | β-1 | β-2 | γ |
|---|---|---|---|---|---|---|
| Lower reference interval (g/l) | 29.00 | 2.08 | 2.94 | 1.54 | 1.51 | 4.33 |
| Upper reference interval (g/l) | 46.70 | 4.99 | 10.25 | 4.50 | 4.90 | 21.40 |
Normal group signalment
The median age of these cats was 7.8 years (range 5 months to 16.5 years). Forty-three males (55.8%) (24 neutered (MN), 19 entire (ME)) and 34 female (44.2%) (18 neutered (FN), 16 entire (FE)) were included. The majority of cats (71.4%) were non-pedigree (53 domestic shorthair, two domestic longhair), with 21 (28.6%) pedigree cats (six Persians, two each of Siamese, Ragdoll, Maine Coon, Burmese, Birman, and one each of Bengal, Tonkinese, Russian Blue, Oriental, Chinchilla) and one cat of unknown breed.
Clinical group signalment
During the study period 160 SPE tests were performed but five were excluded due to non-availability of case records. The median age of the 155 cats in the clinical group was 4.0 years (range 3 months to 16 years). The clinical group included 102 male cats (65.8%) (90 MN, 12 ME) and 53 female cats (34.2%) (40 FN, 13 FE). Breeds included 74 non-pedigrees (50.3%) (65 domestic shorthair, nine domestic longhair) and 81 pedigree cats (49.7%) (13 Siamese, 12 Birman, 11 Burmese, eight Persians, seven Bengals, seven Maine Coons, four Ragdolls, four Abyssinians, four British Shorthairs, three Balinese, three Oriental, two Devon Rex, two Tonkinese and one Somali).
Signalment comparisons between normal and clinical groups
There was no significant difference in the sex distribution between the normal group and the clinical group (P=0.14). However, the normal group contained significantly less pedigree cats (P=0.0014), and was significantly older (P<0.0001), than the clinical group.
SPE results from clinical group
Normal SPE results
Nineteen of the 155 (12.3%) cats had SPE results within the reference intervals. Nine of these cases had ND made. The remaining 10 cats were classified according to the DAMNITV scheme as: metabolic disease in three cats (hepatic disease (one), acute renal failure (one), chronic renal failure (one)), neoplastic disease in one cat (thymoma), infectious/inflammatory disease in five cats (FIP confirmed (two), mycobacterial infection (one), pancreatitis (one), herpesvirus infection (one)) and miscellaneous disease in one cat (dilated cardiomyopathy (DCM)).
Abnormal SPE results
The abnormal SPE results are shown in Tables 2ad; 136/155 (87.7%) cats had abnormal SPE results. Twenty-three cases had ND made. The most common DAMNITV diagnosis classification was inflammatory/infectious disease (total 83 cases; including 39 with FIP − 19 confirmed, 20 suspected). The next most frequent group was neoplasia (14 cases) followed by miscellaneous disease (nine cases). Table 2a–d also list expanded diagnoses for the 136 cats within each DAMNITV category.
Table 2a.
Diagnoses for cats with abnormal SPE results (albumin abnormalities), organised according to the DAMNITV system. 20 Categories with no cases are not illustrated (degenerative, traumatic). Cases with more than one SPE abnormality feature in all relevant categories/rows. Cases with >1 diagnosis within the same DAMNITV category are illustrated in bold type. Cases with >1 diagnosis in different DAMNITV categories are illustrated in italics in all relevant categories/columns but count as one case to the total cases with each SPE abnormality.
| SPE abnormality/DAMNITV group | Total cases (% of 136 cats) | No diagnosis reached (total cases=23) | Anomalous (total cases=5) | Metabolic (total cases=4) | Neoplastic (total cases=14) | Infectious/inflammatory (total cases=83 cases) | Vascular (total cases=3) | Traumatic (total cases=1) | Miscellaneous (total cases=9) |
|---|---|---|---|---|---|---|---|---|---|
| Increased Albumin | 0 (0.0) | ||||||||
| Decreased Albumin | 71 (52.2) | 9 | PSS (3) | Hepatic lipidosis (1) | Pulmonary adenocarcinoma (2) Lymphoma (3) Myeloid leukaemia/FIV positive (1) | FIP (confirmed) (13) FIP (suspected) (20) IBD (lymphoplasmacytic) (1) IBD (lymphoplasmacytic)/FIV positive (1) Ollulanus tricuspis infection (1) Severe neutrophilic dermatitis (agent unknown) (1) Neutrophilic cholangitis (1) Myeloproliferative disease (FIV positive) (1) Herpesvirus/chlamydophila felis (1) Pancreatitis (1) Acute enteritis (agent unknown) (1) Bartonella infection (1) Uveitis (cause unknown) (1) Mycobacterial infection (M microti) (1) Lymphoproliferative rhinitis/chronic airway disease (1) Myeloid leukaemia/FIV positive (1) | Idiopathic glomerular nephropathy (1) Chylothorax (2) DCM (1) Colonic intussusception (1) Megaoesophagus (cause unknown) (1) |
FIP = feline infectious peritonitis, IBD = inflammatory bowel disease, DCM = dilated cardiomyopathy, PSS = portosystemic shunt, IMHA = immune mediated haemolytic anaemia, CNS = central nervous system.
Table 2b.
Diagnoses for cats with abnormal SPE results (α globulin abnormalities), organised according to the DAMNITV system. 20 Categories with no cases are not illustrated (degenerative, traumatic). Cases with more than one SPE abnormality feature in all relevant categories/rows. Cases with >1 diagnosis within the same DAMNITV category are illustrated in bold type. Cases with >1 diagnosis in different DAMNITV categories are illustrated in italics in all relevant categories/columns but count as one case to the total cases with each SPE abnormality.
| SPE abnormality/DAMNITV group | Total cases (% of 136 cats) | No diagnosis reached (total cases=23) | Anomalous (total cases=5) | Metabolic (total cases=4) | Neoplastic (total cases=14) | Infectious/inflammatory (total cases=83 cases) | Vascular (total cases=3) | Traumatic (total cases=1) | Miscellaneous (total cases=9) |
|---|---|---|---|---|---|---|---|---|---|
| Increased α-1 | 16 (11.8) | 3 | PSS (1) | Hyperthyroidism/hypertension (1) Chronic renal failure and pyelonephritis (1) | Forebrain mass (presumed neoplastic) (1) | FIP (confirmed) (1) FIP (strong clinical suspicion) (1) IBD (lymphoplasmacytic)/FIV positive (1) IBD (lymphoplasmacytic)/intestinal polyp (1) Otitis media (1) Inflammatory pulmonary disease/chronic diaphragmatic hernia (1) Uveitis (cause unknown) (1) Chronic renal failure and pyelonephritis (1) | Hyperthyroidism/hypertension (1) | Inflammatory pulmonary disease/chronic diaphragmatic hernia (1) | Chylothorax (2) |
| Decreased α-1 | 3 (2.2) | FIP (confirmed) (1) FIP (suspected) (2) | |||||||
| Increased α-2 | 10 (7.4) | 2 | FIP (confirmed) (1) FIP (suspected) (4) Pyogranulomatous pneumonia (mycobacteria suspected) (1) Inflammatory pulmonary disease/chronic diaphragmatic hernia (1) Uveitis (1) | Inflammatory pulmonary disease/chronic diaphragmatic hernia (1) | |||||
| Decreased α-2 | 3 (2.2) | 1 | Hepatic lipidosis (1) | Lymphoma (1) |
FIP = feline infectious peritonitis, IBD = inflammatory bowel disease, DCM = dilated cardiomyopathy, PSS = portosystemic shunt, IMHA = immune mediated haemolytic anaemia, CNS = central nervous system.
Table 2c.
Diagnoses for cats with abnormal SPE results (β globulin abnormalities), organised according to the DAMNITV system. 20 Categories with no cases are not illustrated (degenerative, traumatic). Cases with more than one SPE abnormality feature in all relevant categories/rows. Cases with >1 diagnosis within the same DAMNITV category are illustrated in bold type. Cases with >1 diagnosis in different DAMNITV categories are illustrated in italics in all relevant categories/columns but count as one case to the total cases with each SPE abnormality.
| SPE abnormality/DAMNITV group | Total cases (% of 136 cats) | No diagnosis reached (total cases=23) | Anomalous (total cases=5) | Metabolic (total cases=4) | Neoplastic (total cases=14) | Infectious/inflammatory (total cases=83 cases) | Vascular (total cases=3) | Traumatic (total cases=1) | Miscellaneous (total cases=9) |
| Increased β-1 | 1 (0.7) | FIP (suspected) | |||||||
| Decreased β-1 | 31 (22.8) | 5 | PSS (1) Calicivirus infection/nasopharyngeal stenosis (1) | Hepatic lipidosis (1) | Pulmonary carcinoma (1) Thyroid carcinoma (1) Lymphoma (1) Splenic plasmacytoma (1) Haemangiosarcoma/paraneoplastic pemphigus foliaceous (1) | FIP (confirmed) (3) FIP (suspected) (2) IBD (lymphoplasmacytic) (2) IMHA (1) Dermatophytosis (1) Calicivirus/nasopharyngeal stenosis (1) Bacterial bronchopneumonia (1) Ollulanus tricuspis infection (1) Alternaria osteomyelitis (1) Mycobacterial infection (1) Haemangiosarcoma/paraneoplastic pemphigus foliaceous (1) | Cerebral infarcts (1) | Idiopathic megacolon (1) Idiopathic glomerular nephropathy (1) Laryngeal paralysis (1) Megaoesophagus (cause unknown) (1) | |
| Increased β-2 | 3 (2.2) | 1 | Lymphoma (1) | Lymphadenitis (S aureus) (1) | |||||
| Decreased β-2 | 12 (8.8) | 3 | PSS (1) | Congenital nephrogenic diabetes insipidus (1) | FIP (confirmed) (1) FIP (suspected) (1) IBD (lymphoplasmacytic) (1) FIV (1) Bacterial bronchopneumonia (1) Neutrophilic dermatitis (cause unknown) (1) | Chylothorax (1) |
FIP = feline infectious peritonitis, IBD = inflammatory bowel disease, DCM = dilated cardiomyopathy, PSS = portosystemic shunt, IMHA = immune mediated haemolytic anaemia, CNS = central nervous system.
Table 2d.
Diagnoses for cats with abnormal SPE results (γ globulin abnormalities), organised according to the DAMNITV system. 20 Categories with no cases are not illustrated (degenerative, traumatic). Cases with more than one SPE abnormality feature in all relevant categories/rows. Cases with >1 diagnosis within the same DAMNITV category are illustrated in bold type. Cases with >1 diagnosis in different DAMNITV categories are illustrated in italics in all relevant categories/columns but count as one case to the total cases with each SPE abnormality.
| SPE abnormality/DAMNITV group | Total cases (% of 136 cats) | No diagnosis reached (total cases=23) | Anomalous (total cases=5) | Metabolic (total cases=4) | Neoplastic (total cases=14) | Infectious/inflammatory (total cases=83 cases) | Vascular (total cases=3) | Traumatic (total cases=1) | Miscellaneous (total cases=9) |
| Increased γ | 81 (59.6) | 8 | PSS (1) Calicivirus/nasopharyngeal stenosis (1) | Hyperthyroidism/hypertension (1) Chronic renal failure and pyelonepritis (1) | Pulmonary carcinoma (1) Myeloid leukaemia/FIV (1) Lymphoma (3) Splenic plasmacytoma (confirmed) (1) Splenic plasmacytoma (suspected) (1) | FIP (suspected) (21) FIP (confirmed) (14) IBD (neutrophilic/lymphocytic) (1) IBD (lymphoplasmacytic) (2) Endocarditis (1) Dermatophytosis (1) Non-healing wound (1) Neutrophilic cholangitis (1) Pyogranulomatous pneumonia (mycobacteria suspected) (1) Calicivirus/nasopharyngeal stenosis (1) Uveitis (cause unknown) (1) Chronic renal failure and pyelonephritis (1) Myeloproliferative disease (FIV positive) (1) IMHA (1) Otitis media (1) Lymphoproliferative rhinitis/chronic airway disease (1) Lymphadenitis (S aureus) (1) Lymphadenitis (cause unknown) (1) Lymphoid hyperplasia and inflammatory skin disease (1) Inflammatory CNS disease (1) Ollulanus tricuspis infection (1) Alternaria osteomyelitis (1) Chronic rhinitis/FIV positive (1) Pancreatitis (2) Myeloid leukaemia/FIV (1) Gingivitis and cerebellar infarcts (1) | Hyperthyroidism/hypertension (1) Gingivitis and cerebellar infarcts (1) | Bone marrow disorder (red cell maturation arrest) (1) Colonic intussusception (1) Megaoesophagus (cause unknown) (1) | |
| Decreased γ | 3 (2.2) | Hepatic lipidosis (1) | Lymphoma (1) | Chylothorax (1) |
FIP = feline infectious peritonitis, IBD = inflammatory bowel disease, DCM = dilated cardiomyopathy, PSS = portosystemic shunt, IMHA = immune mediated haemolytic anaemia, CNS = central nervous system.
The most common SPE abnormalities detected were increased γ globulins (81/136 cases, 59.6%) and decreased albumin (71/136 cases, 52.2%). Seventy-four of the 136 (54.4%) cats had more than one SPE abnormality with the most common pattern being increased γ globulins with decreased albumin. Of the 46 cats with this SPE pattern, 35 had infectious/inflammatory disease.
Of the 81 cats with increased γ globulins the majority (77; 95.1%) had a polyclonal pattern (Fig 2) whilst the remaining four cats had monoclonal gammopathies. One cat had a monoclonal spike within a polyclonal elevation (Fig 3) and was diagnosed with FIP (confirmed). The remaining three cats had a spike in the γ region taller than the albumin spike and with a narrow base (Fig 4): one cat with intestinal and hepatic lymphoma and two had splenic plasmacytomas (histopathologically confirmed in one and suspected in the other; with a large reduction in the γ globulin spike documented 1 week post-splenectomy in the suspected case as shown in Fig 4).
Fig 2.
SPE densitometer trace illustrating a polyclonal gammopathy and spike in the α-2 region in a cat with confirmed FIP. The majority of cats with FIP in this study had increased γ globulins with a polyclonal trace.
Fig 3.
SPE densitometer trace from a cat with confirmed FIP illustrating a polyclonal, wide based gammopathy with a monoclonal ‘spike’ in the γ region. This trace also shows an increase in α-2 globulins.
Fig 4.
SPE densitometer trace illustrating a monoclonal gammopathy in a cat with a suspected splenic plasmacytoma at diagnosis (red line) and 1 week post-splenectomy (black line).
Further description of cases diagnosed with FIP
The majority of cats in the FIP group had abnormal SPE results (39/41 cases, 95.1%). The most common abnormality was increased γ globulins (35/41 cases, 85.4%) and decreased albumin (33/41 cases, 80.5%). Decreased β-1 globulins (5/41 cases, 12.2%) and increased α-2 globulins (5/41 cases, 12.2%) were observed less frequently.
Discussion
In humans SPE is mainly used to identify patients with multiple myeloma and to investigate serum dysproteinaemias. 4 Others have suggested its use in gastroenterology with typical electrophoretic patterns seen in chronic liver disease and inflammatory bowel disease (IBD). 22 In veterinary medicine indications for performing SPE have largely centred on the investigation of hyperproteinaemia, screening for monoclonal gammopathies and characterisation of hypoproteinaemias (particularly when immunodeficiencies are suspected). 1,3
Sparse information regarding feline SPE has been published and that which has been published has usually involved brief descriptions of SPE results within papers containing case clinical data. Normal ranges have been reported 23–26 and the SPE changes associated with FIP 8–10 , FIV/FeLV 11 and multiple myeloma 12,13 investigated. Reports of SPE abnormalities associated with other infectious diseases such as ehrlichiosis and anaplasma, 16,17 and individual case reports 27–29 have also been published. To the authors’ knowledge this is the first study to specifically focus on SPE results in cats and retrospectively examine SPE results from a large referral hospital cat population, and to describe all the disease processes associated with the SPE abnormalities.
Electrophoresis methodology may vary between laboratories 3 so a laboratory specific reference interval was created for evaluation of the clinical cases in the current study. Ideally, a reference interval is created using well-defined healthy subjects, representative of the reference population. 19 In the current study, the reference intervals were created using excess serum from samples submitted as part of the Pet Travel Scheme, as in the UK sampling of healthy animals without other indication is prohibited. These ‘normal’ cats were of a range of ages and breeds and reported to be clinically healthy. However, it was not possible to control factors such as geographical location, environment, stress and the possibility of occult disease, and these may have led to influences on the SPE results. Indeed, environmental and geographical variations in SPE results from normal cats have been previously reported, presumably due to varied antigenic stimulus. 23,24 The normal group were significantly older and contained fewer pedigree cats than the clinical group and, therefore, was not as representative of the clinical group as intended. However, the reference interval created was still used as this was felt to be the best compromise due to the limited availability of samples for the normal group.
In the present study the diagnoses were grouped according to the DAMNITV classification as has been previously used. 20,21 This classification is arbitrary but simplifies the data to allow the reader to assess the SPE abnormalities associated with each category of disease and conversely the diseases associated with specific SPE abnormalities. The subjective assessment of retrospective data is a limitation of the current study.
The large number of abnormal SPE results in the clinical group (87.7%) may be partly due to case selection. It is likely that clinicians request SPE once hyperproteinaemia has been confirmed or if a disease associated with SPE abnormalities, such as FIP or plasma cell neoplasia, is suspected, increasing the likelihood of SPE abnormalities in the clinical group. Variation between attending clinicians in choice of diagnostic test may also have affected case selection.
In the present study most FIP cases had increased γ globulins, as previously reported. 8–10 A concurrent increase in α-2 globulins, reported in 71% of cases in a previous study, 9 was only found in 12.2% of the current cases, suggesting that APPs such as haptoglobin are not consistently elevated in FIP, although reference intervals for the previously mentioned study were not available for comparison. A limitation of the current study is the lack of histological confirmation of FIP in all cases but confirmed and suspected cases showed the same electrophoretic patterns (polyclonal gammopathies and infrequent increase in α-2). The gammopathy was polyclonal in all but one FIP case which exhibited a monoclonal spike in the γ region (Fig 3). Polyclonal gammopathies are reported in the majority of FIP cases, 8–10 however, six cats with monoclonal gammopathies and confirmed FIP have previously been reported, 14,15,18 suggesting FIP should be considered as a differential diagnosis for monoclonal gammopathies in cats.
In the current study the finding of a monoclonal gammopathy was unusual (only 4/155 cats). As well as the cat with FIP described previously, plasma cell neoplasia was diagnosed in one case and suspected in another and the remaining cat with a monoclonal gammopathy was diagnosed with lymphoma. Multiple myeloma is a form of multifocal plasma cell neoplasia involving the bone marrow. Other forms of plasma cell neoplasia without bone marrow involvement are termed extramedullary plasmacytoma and can involve the skin and/or internal organs as seen in the present study. 13 In a recent study of myeloma-related disorders in cats, Mellor et al found that the extramedullary form was more common in cats than humans or dogs, with abdominal organ involvement seen frequently in these cases. 13 The majority of these cases exhibited a monoclonal gammopathy emphasising the need to investigate cats with monoclonal gammopathies for extramedullary plasmacytoma as well as multiple myeloma. Monoclonal gammopathies have been reported infrequently associated with lymphoma in cats, 27,28 and lymphoplasmacytic stomatitis 29 and have also occasionally been reported in cats with infectious diseases such as ehrlichiosis/anaplasmosis. 16,17 In dogs, monoclonal gammopathies are equally unusual and most frequently associated with lymphoproliferative disease, 6 but also reported in association with various infectious/inflammatory conditions including ehrlichiosis, 6,30 leishmaniasis, 6,7 pyoderma, 31 plasmacytic gastroenterocolitis 32 and Waldenström's macroglobulinaemia.33
A limitation of the current study is the lack of immunoelectrophoresis to confirm the immunoglobulin subtype and monoclonal nature of such gammopathies. Without immunoelectrophoresis, a suspected monoclonal gammopathy cannot reliably be differentiated from a restricted or compact polyclonal or oligoclonal gammopathy. 1,5 However, as immunoelectrophoresis has limited availability to practitioners, the description of diseases resulting in a monoclonal spike on the electrophoresis trace remains useful.
Polyclonal gammopathies occurred with many infectious/inflammatory diseases other than FIP in the current study demonstrating the lack of specificity of SPE as a diagnostic test for FIP as has been previously reported, 9 and illustrating the limitations of this technique as diagnostic aid.
A polyclonal gammopathy with concurrent reduced albumin was the most common electrophoretic pattern; documented in 33.8% of cases, and is consistent with persistent antigenic stimulation and compensatory reduction in albumin concentration to maintain oncotic pressure/viscosity. 3 A wide variety of infectious/inflammatory diseases produced this pattern, such as bacterial, viral, fungal and parasitic diseases, as well as presumed immune-mediated conditions such as IBD and immune-mediated haemolytic anaemia (IMHA).
Decreased β globulins (either β-1 or β-2 or both) occurred in 31.6% of cases, with infectious/inflammatory disease the most common diagnosis, which is in contrast to the situation in humans where protein malnutrition most commonly causes decreased β globulins. 4,22
In conclusion, this study found that the most common abnormality detected by SPE in cats referred to a veterinary hospital was a polyclonal increase in γ globulins. Infectious/inflammatory diseases made up the largest disease category amongst cases with abnormal SPE results. Monoclonal globulin increases were unusual and observed in association with neoplasia and FIP.
Acknowledgements
SST currently holds a position sponsored by Pfizer Animal Health, and previously was funded by the Feline Advisory Bureau. Data included in this article have been previously presented as an abstract at the 15th annual European College of Veterinary Internal Medicine (ECVIM) Congress, Glasgow, UK, 2005. 34 The authors would like to thank Dr Susan Shaw of The University of Bristol and Professor AR Fooks of The Veterinary Laboratories Agency for providing the samples from normal animals.
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