blood analysis

ANCA - Neutrophil Cytoplasmic Antibodies

Generality

Neutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against antigens contained in the granulocyte cytoplasm.

Their presence is a useful serological marker for the diagnosis and monitoring of some systemic autoimmune diseases; these include primary vasculitis (inflammation of the vessels), such as:

  • Wegener's granulomatosis;
  • Microscopic polyangiitis;
  • Churg-Strauss syndrome.

The ANCA can also contribute to the diagnosis of inflammatory bowel diseases (in particular, in the distinction between Crohn's disease and ulcerative colitis) and sclerosing cholangitis.

What are

ANCAs are autoantibodies to cytoplasmic constituents of neutrophil granulocytes .

What are autoantibodies?

Auto-antibodies are immunoglobulins directed against healthy and normal molecular and cellular structures of the organism, wrongly interpreted as dangerous antigens, therefore considered worthy of an immune attack.

The great majority of autoimmune diseases have in common, with particular specificities, the finding of these antibodies; this means that raising their blood values ​​is an indicator that indicates the possible presence of a certain disease.

Thus, auto-antibodies such as ANCA represent fundamental markers for the diagnosis (and sometimes for the prognosis) of these autoimmune diseases.

The main antigenic targets of neutrophil cytoplasmic antibodies are:

  • Myeloperoxidase (MPO) : enzyme with important bactericidal properties, which exerts through the catalysis of peroxidation reactions and the formation of toxic products, such as hypochlorous acid (HClO), hydrogen peroxide (H 2 O 2 ) and oxygen radicals. Furthermore, hypochlorous acid and its metabolites can inactivate protease inhibitors, playing a role in maintaining an "inflammatory" microenvironment. MPO represents about 5% of the total protein content of neutrophils.
  • Proteinase 3 (PR 3): serine-protease contained in primary (or azure) granulocyte and monocyte granules, with antimicrobial activity against bacteria and fungi. Most of its biological functions depend on proteolytic activity. In an inflammatory context, PR 3 is released outside the cell, together with other constituents of the granules and oxygen radicals, where it can degrade collagen, proteoglycans and other constituents of connective tissue. Excessive, prolonged or inappropriate proteolytic activity, however, causes damage to the organism.

Because they measure themselves

The neutrophil cytoplasmic antibody (ANCA) assay detects the presence of these autoantibodies in the blood. This finding may be related to some autoimmune disorders.

Systemic vasculitis

The ANCA exam is mainly used as a test to support the diagnosis of some vasculitis, small and medium caliber vessels, including:

  • Wegener's granulomatosis;
  • Microscopic polyangiitis;
  • Narcotonologic extracapillary pauci-immune glomerulonephritis (a form of microscopic polyangiitis limited to the kidney);
  • Churg-Strauss syndrome.

These conditions are often collectively referred to as "vasculitis-ANCA-associated".

Other pathologies

The ANCA dosage is also useful in distinguishing between Crohn's disease and ulcerative colitis, the two most common forms of inflammatory bowel diseases.

Associated examinations

In relation to the signs and symptoms that the patient manifests and the suspected pathology, the ANCA test can be associated with other investigations, such as:

  • Blood cell count;
  • Urine tests;
  • Dosage of urea and creatinine;
  • Evaluation of erythrocyte sedimentation rate (ESR) and / or C-reactive protein (PCR).

In many cases, a biopsy of the vessel involved in the disease process is required to diagnose vasculitis.

ANCA can be prescribed together with ASCA (anti-Saccharomyces cerevisiae antibodies), when the subject shows symptoms of inflammatory bowel disease and the clinician must distinguish between Crohn's disease and ulcerative colitis.

Normal values

Normally, the search for anti-cytoplasmic neutrophil antibodies provides a negative outcome (ANCA: absent).

ANCA Alti - Causes

ANCA may be present in a variety of autoimmune diseases, characterized by widespread inflammatory lesions in numerous organs and systems.

Some types of vasculitis are closely associated with the production of ANCA. These conditions include the following systemic forms:

  • Wegener's granulomatosis (or granulomatosis associated with polyangiitis);
  • Microscopic polyangiitis;
  • Narcotonologic extracapillary pauci-immune glomerulonephritis (a form of microscopic polyangiitis limited to the kidney);
  • Churg-Strauss syndrome;
  • Polyarteritis nodosa (PAN).

Vasculitis is a heterogeneous group of diseases, characterized by damage and weakening of blood vessels, associated with the infiltration of inflammatory cells and necrosis of vascular walls. The consequences of inflammation depend on the size, location and number of blood vessels involved.

At the onset, vasculitis generally involves the following symptoms:

  • Temperature;
  • Muscle pains;
  • Weight loss;
  • Night sweats;
  • Fatigue.

The reduced vascular flow can determine consequences in various organs (such as kidneys, lungs and skin), as well as predispose to the formation and rupture of aneurysms.

As for inflammatory bowel diseases, ANCAs are usually associated with ulcerative colitis (80% of cases), while only 20% of Crohn's disease patients are usually positive.

Other conditions that may be related to the detection of ANCA antibodies include:

  • Rheumatoid arthritis;
  • Systemic lupus erythematosus;
  • Autoimmune hepatitis;
  • Use of some drugs;
  • Endocarditis;
  • Lung diseases and inflammation of the respiratory system.

HIP Bass - Causes

A negative ANCA test suggests that an autoimmune disorder is unlikely. If symptoms recur, however, it may be useful to repeat the exam.

If low levels of neutrophil cytoplasmic antibodies are found, the doctor will establish the diagnosis once all the data needed are collected.

How to measure it

For ANCA analysis, the patient must have blood drawn from a vein in his arm.

The determination of these autoantibodies foresees the standard method of indirect immunofluorescence (IFI), to which is associated the confirmation test ELISA (enzyme linked immunosorbent assay) specific antigen.

  • IFI (indirect immunofluorescence assay): the patient's blood sample is mixed with the cells that are attached to the slide. Autoantibodies that are present in the blood react with cells. The slide is treated with a reagent containing fluorescent antibodies and examined under a microscope. What is observed is the presence (or absence) of fluorescence.
  • ELISA : it is performed with automated instruments, but it is less sensitive than the indirect immunofluorescence assay in the determination of the ANCA.

The combination of the two tests (IFI + ELISA) increases the specificity up to almost 100% for the diagnosis of primitive systemic vasculitis.

Preparation

Before undergoing the examination, the patient must observe a fast of at least 8-10 hours, during which a small quantity of water is allowed.

Interpretation of Results

The result of the ANCA must be interpreted carefully, taking into account the clinical signs and other tests, such as diagnostic imaging.

Vasculitis

Using the IFI method, two main panels can be recognized:

  • cANCA / PR3 : diffuse granular cytoplasmic fluoroscopic staining. This pattern is associated in 90-95% of cases with the presence of PR3-ANCA specific autoantibodies, mainly found in Wegener's granulomatosis .
  • pANCA / MPO : perinuclear and / or nuclear staining caused in about 80% of cases by the presence of MPO-ANCA. These antibodies are most frequently associated with microscopic forms of polyangiitis (polyarteritis nodosa and Churg-Strauss syndrome), chronic intestinal diseases and sclerosing cholangitis .

At times, examination of anti-cytoplasmic neutrophil antibodies can be used to monitor therapy and / or to reveal recurrences of these pathologies.

Inflammatory bowel disease

A further variant, called x-ANCA, can be found in the course of many diseases, but in particular it is frequent in inflammatory bowel diseases.

The finding of atypical ANCA is supportive in the differential diagnosis between ulcerative colitis and Crohn's disease. As a rule, the presence of these auto-antibodies is mainly associated with ulcerative colitis (ANCA is found in 80% of cases). Neutrophil cytoplasmic antibodies are found in only 20% of patients with Crohn's disease.

In cases where ANCA results positive and anti-Saccharomyces cerevisiae negative (ASCA) antibodies, it is possible that the patient has ulcerative colitis. In the opposite case, ie the ANCA are negative and the ASCA positive, the presence of Crohn's disease is likely.

It should be noted, however, that the patient suffering from one of these inflammatory bowel diseases may not be positive for the search for such auto-antibodies.